, Volume 14, Issue 3, pp 588–613 | Cite as

From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms

  • Zeeba D. Kabir
  • Arlene Martínez-Rivera
  • Anjali M. Rajadhyaksha


The L-type calcium channels (LTCCs) Cav1.2 and Cav1.3, encoded by the CACNA1C and CACNA1D genes, respectively, are important regulators of calcium influx into cells and are critical for normal brain development and plasticity. In humans, CACNA1C has emerged as one of the most widely reproduced and prominent candidate risk genes for a range of neuropsychiatric disorders, including bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder, autism spectrum disorder, and attention deficit hyperactivity disorder. Separately, CACNA1D has been found to be associated with BD and autism spectrum disorder, as well as cocaine dependence, a comorbid feature associated with psychiatric disorders. Despite growing evidence of a significant link between CACNA1C and CACNA1D and psychiatric disorders, our understanding of the biological mechanisms by which these LTCCs mediate neuropsychiatric-associated endophenotypes, many of which are shared across the different disorders, remains rudimentary. Clinical studies with LTCC blockers testing their efficacy to alleviate symptoms associated with BD, SCZ, and drug dependence have provided mixed results, underscoring the importance of further exploring the neurobiological consequences of dysregulated Cav1.2 and Cav1.3. Here, we provide a review of clinical studies that have evaluated LTCC blockers for BD, SCZ, and drug dependence-associated symptoms, as well as rodent studies that have identified Cav1.2- and Cav1.3-specific molecular and cellular cascades that underlie mood (anxiety, depression), social behavior, cognition, and addiction.


Cav1.2 Cav1.3 CACNA1C CACNA1D Mood Social Addiction 

Supplementary material

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  1. 1.
    Kabir ZD, Lee AS, Rajadhyaksha AM. L-type Ca2+ channels in mood, cognition and addiction: integrating human and rodent studies with a focus on behavioural endophenotypes. J Physiol 594(20), 5823-5837 (2016).PubMedCrossRefGoogle Scholar
  2. 2.
    Zamponi GW, Striessnig J, Koschak A, Dolphin AC. The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol Rev 67(4), 821-870 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ebert DH, Greenberg ME. Activity-dependent neuronal signalling and autism spectrum disorder. Nature 493(7432), 327-337 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bhat S, Dao DT, Terrillion CE, et al. CACNA1C (Cav1.2) in the pathophysiology of psychiatric disease. Prog Neurobiol 99(1), 1-14 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Heyes S, Pratt WS, Rees E, et al. Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders. Prog Neurobiol 2015; 134:35-54.CrossRefGoogle Scholar
  6. 6.
    Ortner NJ, Striessnig J. L-type calcium channels as drug targets in CNS disorders. Channels (Austin) 10(1), 7-13 (2016).CrossRefGoogle Scholar
  7. 7.
    Pinggera A, Lieb A, Benedetti B, et al. CACNA1D de novo mutations in autism spectrum disorders activate Cav1.3 L-type calcium channels. Biol Psychiatry 77(9), 816-822 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Romme IA, de Reus MA, Ophoff RA, Kahn RS, van den Heuvel MP. Connectome disconnectivity and cortical gene expression in patients with schizophrenia. Biol Psychiatry 81(6), 495-502 (2017).PubMedCrossRefGoogle Scholar
  9. 9.
    Gurung R, Prata DP. What is the impact of genome-wide supported risk variants for schizophrenia and bipolar disorder on brain structure and function? A systematic review. Psychol Med 45(12), 2461-2480 (2015).PubMedCrossRefGoogle Scholar
  10. 10.
    Striessnig J, Pinggera A, Kaur G, Bock G, Tuluc P. L-type Ca(2+) channels in heart and brain. Wiley Interdiscip Rev Membr Transp Signal 3(2), 15-38 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Tanaka O, Sakagami H, Kondo H. Localization of mRNAs of voltage-dependent Ca(2+)-channels: four subtypes of alpha 1- and beta-subunits in developing and mature rat brain. Brain Res Mol Brain Res 30(1), 1-16 (1995).PubMedCrossRefGoogle Scholar
  12. 12.
    Ludwig A, Flockerzi V, Hofmann F. Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain. J Neurosci 17(4), 1339-1349 (1997).PubMedGoogle Scholar
  13. 13.
    Herman JP, Chen KC, Booze R, Landfield PW. Up-regulation of alpha1D Ca2+ channel subunit mRNA expression in the hippocampus of aged F344 rats. Neurobiol Aging 19(6), 581-587 (1998).PubMedCrossRefGoogle Scholar
  14. 14.
    Clark NC, Nagano N, Kuenzi FM, et al. Neurological phenotype and synaptic function in mice lacking the CaV1.3 alpha subunit of neuronal L-type voltage-dependent Ca2+ channels. Neuroscience 120(2), 435-442 (2003).PubMedCrossRefGoogle Scholar
  15. 15.
    Rajadhyaksha A, Husson I, Satpute SS, et al. L-type Ca2+ channels mediate adaptation of extracellular signal-regulated kinase 1/2 phosphorylation in the ventral tegmental area after chronic amphetamine treatment. J Neurosci 24(34), 7464-7476 (2004).PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Bernardi RE, Uhrig S, Spanagel R, Hansson AC. Transcriptional regulation of L-type calcium channel subtypes Cav1.2 and Cav1.3 by nicotine and their potential role in nicotine sensitization. Nicotine Tob Res 16(6), 774-785 (2014).PubMedCrossRefGoogle Scholar
  17. 17.
    Liebmann L, Karst H, Sidiropoulou K, et al. Differential effects of corticosterone on the slow afterhyperpolarization in the basolateral amygdala and CA1 region: possible role of calcium channel subunits. J Neurophysiol 99(2), 958-968 (2008).PubMedCrossRefGoogle Scholar
  18. 18.
    Brewer LD, Dowling AL, Curran-Rauhut MA, Landfield PW, Porter NM, Blalock EM. Estradiol reverses a calcium-related biomarker of brain aging in female rats. J Neurosci 29(19), 6058-6067 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Daschil N, Kniewallner KM, Obermair GJ, et al. L-type calcium channel blockers and substance P induce angiogenesis of cortical vessels associated with beta-amyloid plaques in an Alzheimer mouse model. Neurobiol Aging 36(3), 1333-1341 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Uhrig S, Vandael D, Marcantoni A, et al. Differential roles for L-type calcium channel subtypes in alcohol dependence. Neuropsychopharmacology 2017;42:1058-1069.PubMedCrossRefGoogle Scholar
  21. 21.
    Hetzenauer A, Sinnegger-Brauns MJ, Striessnig J, Singewald N. Brain activation pattern induced by stimulation of L-type Ca2+-channels: contribution of Ca(V)1.3 and Ca(V)1.2 isoforms. Neuroscience 139(3), 1005-1015 (2006).Google Scholar
  22. 22.
    Catterall WA. Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16, 521-555 (2000).PubMedCrossRefGoogle Scholar
  23. 23.
    Xu W, Lipscombe D. Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J Neurosci 21(16), 5944-5951 (2001).Google Scholar
  24. 24.
    Lipscombe D. L-type calcium channels: highs and new lows. Circ Res 90(9), 933-935 (2002).PubMedCrossRefGoogle Scholar
  25. 25.
    Koschak A, Reimer D, Huber I, et al. alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages. J Biol Chem, 276(25), 22100-22106 (2001).PubMedCrossRefGoogle Scholar
  26. 26.
    Simms BA, Zamponi GW. Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron, 82(1), 24-45 (2014).PubMedCrossRefGoogle Scholar
  27. 27.
    Calin-Jageman I, Lee A. Ca(v)1 L-type Ca2+ channel signaling complexes in neurons. J Neurochem, 105(3), 573-583 (2008).PubMedCrossRefGoogle Scholar
  28. 28.
    Stanika R, Campiglio M, Pinggera A, et al. Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology. Sci Rep 6, 34528 (2016).Google Scholar
  29. 29.
    Zamponi GW. Targeting voltage-gated calcium channels in neurological and psychiatric diseases. Nat Rev Drug Discov 15(1), 19-34 (2016).PubMedCrossRefGoogle Scholar
  30. 30.
    Striessnig J, Ortner NJ, Pinggera A. Pharmacology of L-type calcium channels: novel drugs for old targets? Curr Mol Pharmacol 8(2), 110-122 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Ament SA, Szelinger S, Glusman G, et al. Rare variants in neuronal excitability genes influence risk for bipolar disorder. Proc Natl Acad Sci U S A 112(11), 3576-3581 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Nyegaard M, Demontis D, Foldager L, et al. CACNA1C (rs1006737) is associated with schizophrenia. Mol Psychiatry 15(2), 119-121 (2010).PubMedCrossRefGoogle Scholar
  33. 33.
    Rao S, Yao Y, Zheng C, et al. Common variants in CACNA1C and MDD susceptibility: a comprehensive meta-analysis. Am J Med Genet B Neuropsychiatr Genet 171(6), 896-903 (2016).PubMedCrossRefGoogle Scholar
  34. 34.
    Li J, Zhao L, You Y, et al. Schizophrenia related variants in CACNA1C also confer risk of autism. PLOS ONE 10(7), e0133247 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381(9875), 1371-1379 (2013).Google Scholar
  36. 36.
    Zhang F, Lupski JR. Non-coding genetic variants in human disease. Hum Mol Genet 24(R1), R102-110 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Roussos P, Mitchell AC, Voloudakis G, et al. A role for noncoding variation in schizophrenia. Cell Rep 9(4), 1417-1429 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Eckart N, Song Q, Yang R, et al. Functional characterization of schizophrenia-associated variation in CACNA1C. PLOS ONE 11(6), e0157086 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Bigos KL, Mattay VS, Callicott JH, et al. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 67(9), 939-945 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Yoshimizu T, Pan JQ, Mungenast AE, et al. Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons. Mol Psychiatry 20(2), 162-169 (2015).PubMedCrossRefGoogle Scholar
  41. 41.
    Gershon ES, Grennan K, Busnello J, et al. A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain. Mol Psychiatry 19(8), 890-894 (2014).PubMedCrossRefGoogle Scholar
  42. 42.
    International Schizophrenia C, Purcell SM, Wray NR, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460(7256), 748-752 (2009).Google Scholar
  43. 43.
    Page KM, Heblich F, Margas W, et al. N terminus is key to the dominant negative suppression of Ca(V)2 calcium channels: implications for episodic ataxia type 2. J Biol Chem 285(2), 835-844 (2010).PubMedCrossRefGoogle Scholar
  44. 44.
    Page KM, Heblich F, Davies A, et al. Dominant-negative calcium channel suppression by truncated constructs involves a kinase implicated in the unfolded protein response. J Neurosci 24(23), 5400-5409 (2004).PubMedCrossRefGoogle Scholar
  45. 45.
    Mezghrani A, Monteil A, Watschinger K, et al. A destructive interaction mechanism accounts for dominant-negative effects of misfolded mutants of voltage-gated calcium channels. J Neurosci 28(17), 4501-4511 (2008).PubMedCrossRefGoogle Scholar
  46. 46.
    Splawski I, Timothy KW, Sharpe LM, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119(1), 19-31 (2004).PubMedCrossRefGoogle Scholar
  47. 47.
    Gillis J, Burashnikov E, Antzelevitch C, et al. Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. Am J Med Genet A 158A(1), 182-187 (2012).PubMedCrossRefGoogle Scholar
  48. 48.
    Splawski I, Timothy KW, Decher N, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci U S A 102(23), 8089-8096 (2005).PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ross J, Gedvilaite E, Badner JA, et al. A rare variant in CACNA1D segregates with 7 bipolar I disorder cases in a large pedigree. Mol Neuropsychiatry 2(3), 145-150 (2016).PubMedCrossRefGoogle Scholar
  50. 50.
    Guan F, Li L, Qiao C, et al. Evaluation of genetic susceptibility of common variants in CACNA1D with schizophrenia in Han Chinese. Sci Rep 5, 12935 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Martinez-Rivera A, Hao J, Tropea TF, et al. Enhancing VTA Cav1.3 L-type Ca2+ channel activity promotes cocaine and mood-related behaviors via overlapping AMPA receptor mechanisms in the nucleus accumbens. Mol Psychiatry 2017 Feb 14 [Epub ahead of print].Google Scholar
  52. 52.
    Iossifov I, O'Roak BJ, Sanders SJ, et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515(7526), 216-221 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    O'Roak BJ, Vives L, Girirajan S, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485(7397), 246-250 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Limpitikul WB, Dick IE, Ben-Johny M, Yue DT. An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation. Sci Rep 6, 27235 (2016).Google Scholar
  55. 55.
    Olson PA, Tkatch T, Hernandez-Lopez S, et al. G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain. J Neurosci 25(5), 1050-1062 (2005).Google Scholar
  56. 56.
    Berkefeld H, Fakler B. Repolarizing responses of BKCa-Cav complexes are distinctly shaped by their Cav subunits. J Neurosci 28(33), 8238-8245 (2008).PubMedCrossRefGoogle Scholar
  57. 57.
    Berkefeld H, Sailer CA, Bildl W, et al. BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling. Science 314(5799), 615-620 (2006).PubMedCrossRefGoogle Scholar
  58. 58.
    Goodnick PJ. Treatment of mania: relationship between response to verapamil and changes in plasma calcium and magnesium levels. South Med J 89(2), 225-226 (1996).PubMedCrossRefGoogle Scholar
  59. 59.
    Wisner KL, Peindl KS, Perel JM, Hanusa BH, Piontek CM, Baab S. Verapamil treatment for women with bipolar disorder. Biol Psychiatry 51(9), 745-752 (2002).PubMedCrossRefGoogle Scholar
  60. 60.
    Lenzi A, Marazziti D, Raffaelli S, Cassano GB. Effectiveness of the combination verapamil and chlorpromazine in the treatment of severe manic or mixed patients. Prog Neuropsychopharmacol Biol Psychiatry 19(3), 519-528 (1995).PubMedCrossRefGoogle Scholar
  61. 61.
    Barton BM, Gitlin MJ. Verapamil in treatment-resistant mania: an open trial. J Clin Psychopharmacol 7(2), 101-103 (1987).PubMedCrossRefGoogle Scholar
  62. 62.
    Garza-Trevino ES, Overall JE, Hollister LE. Verapamil versus lithium in acute mania. Am J Psychiatry 149(1), 121-122 (1992).PubMedCrossRefGoogle Scholar
  63. 63.
    Giannini AJ, Taraszewski R, Loiselle RH. Verapamil and lithium in maintenance therapy of manic patients. J Clin Pharmacol 27(12), 980-982 (1987).PubMedCrossRefGoogle Scholar
  64. 64.
    Dubovsky SL, Franks RD, Allen S. Verapamil: a new antimanic drug with potential interactions with lithium. J Clin Psychiatry 48(9), 371-372 (1987).PubMedGoogle Scholar
  65. 65.
    Solomon L, Williamson P. Verapamil in bipolar illness. Can J Psychiatry 31(5), 442-444 (1986).PubMedCrossRefGoogle Scholar
  66. 66.
    Gitlin MJ, Weiss J. Verapamil as maintenance treatment in bipolar illness: a case report. J Clin Psychopharmacol 4(6), 341-343 (1984).PubMedCrossRefGoogle Scholar
  67. 67.
    Jacques RM, Cox SJ. Verapamil in major (psychotic) depression. Br J Psychiatry 158, 124-125 (1991).PubMedCrossRefGoogle Scholar
  68. 68.
    Dubovsky SL, Franks RD, Allen S, Murphy J. Calcium antagonists in mania: a double-blind study of verapamil. Psychiatry Res 18(4), 309-320 (1986).PubMedCrossRefGoogle Scholar
  69. 69.
    Giannini AJ, Houser WL, Jr., Loiselle RH, Giannini MC, Price WA. Antimanic effects of verapamil. Am J Psychiatry 141(12), 1602-1603 (1984).PubMedCrossRefGoogle Scholar
  70. 70.
    Mallinger AG, Thase ME, Haskett R, et al. Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms. Bipolar Disord 10(8), 856-866 (2008).PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Janicak PG, Sharma RP, Pandey G, Davis JM. Verapamil for the treatment of acute mania: a double-blind, placebo-controlled trial. Am J Psychiatry 155(7), 972-973 (1998).PubMedCrossRefGoogle Scholar
  72. 72.
    Hoschl C, Kozeny J. Verapamil in affective disorders: a controlled, double-blind study. Biol Psychiatry 25(2), 128-140 (1989).PubMedCrossRefGoogle Scholar
  73. 73.
    Ried LD, Tueth MJ, Handberg E, Kupfer S, Pepine CJ; Invest Study Group. A Study of Antihypertensive Drugs and Depressive Symptoms (SADD-Sx) in patients treated with a calcium antagonist versus an atenolol hypertension Treatment Strategy in the International Verapamil SR-Trandolapril Study (INVEST). Psychosom Med 67(3), 398-406 (2005).PubMedCrossRefGoogle Scholar
  74. 74.
    Pazzaglia PJ, Post RM, Ketter TA, et al. Nimodipine monotherapy and carbamazepine augmentation in patients with refractory recurrent affective illness. J Clin Psychopharmacol 18(5), 404-413 (1998).PubMedCrossRefGoogle Scholar
  75. 75.
    Pazzaglia PJ, Post RM, Ketter TA, George MS, Marangell LB. Preliminary controlled trial of nimodipine in ultra-rapid cycling affective dysregulation. Psychiatry Res 49(3), 257-272 (1993).PubMedCrossRefGoogle Scholar
  76. 76.
    Brunet G, Cerlich B, Robert P, Dumas S, Souetre E, Darcourt G. Open trial of a calcium antagonist, nimodipine, in acute mania. Clin Neuropharmacol 13(3), 224-228 (1990).PubMedCrossRefGoogle Scholar
  77. 77.
    Grunze H, Walden J, Wolf R, Berger M. Combined treatment with lithium and nimodipine in a bipolar I manic syndrome. Prog Neuropsychopharmacol Biol Psychiatry 20(3), 419-426 (1996).PubMedCrossRefGoogle Scholar
  78. 78.
    Davanzo PA, Krah N, Kleiner J, McCracken J. Nimodipine treatment of an adolescent with ultradian cycling bipolar affective illness. J Child Adolesc Psychopharmacol 9(1), 51-61 (1999).PubMedCrossRefGoogle Scholar
  79. 79.
    Caillard V. Treatment of mania using a calcium antagonist—preliminary trial. Neuropsychobiology 14(1), 23-26 (1985).PubMedCrossRefGoogle Scholar
  80. 80.
    Silverstone PH, Birkett L. Diltiazem as augmentation therapy in patients with treatment-resistant bipolar disorder: a retrospective study. J Psychiatry Neurosci 25(3), 276-280 (2000).PubMedPubMedCentralGoogle Scholar
  81. 81.
    Hullett FJ, Potkin SG, Levy AB, Ciasca R. Depression associated with nifedipine-induced calcium channel blockade. Am J Psychiatry 145(10), 1277-1279 (1988).PubMedCrossRefGoogle Scholar
  82. 82.
    Price WA, Heil D. Treatment of the negative symptoms of schizophrenia with verapamil. Jefferson Journal of Psychiatry 5(1) (1987).Google Scholar
  83. 83.
    Price WA. Antipsychotic effects of verapamil in schizophrenia. Hillside J Clin Psychiatry 9(2), 225-230 (1987).PubMedGoogle Scholar
  84. 84.
    Uhr SB, Jackson K, Berger PA, Csernansky JG. Effects of verapamil administration on negative symptoms of chronic schizophrenia. Psychiatry Res 23(3), 351-352 (1988).PubMedCrossRefGoogle Scholar
  85. 85.
    Schwartz BL, Fay-McCarthy M, Kendrick K, Rosse RB, Deutsch SI. Effects of nifedipine, a calcium channel antagonist, on cognitive function in schizophrenic patients with tardive dyskinesia. Clin Neuropharmacol 20(4), 364-370 (1997).PubMedCrossRefGoogle Scholar
  86. 86.
    Bartko G, Horvath S, Zador G, Frecska E. Effects of adjunctive verapamil administration in chronic schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 15(3), 343-349 (1991).PubMedCrossRefGoogle Scholar
  87. 87.
    Pickar D, Wolkowitz OM, Doran AR, et al. Clinical and biochemical effects of verapamil administration to schizophrenic patients. Arch Gen Psychiatry 44(2), 113-118 (1987).PubMedCrossRefGoogle Scholar
  88. 88.
    Grebb JA, Shelton RC, Taylor EH, Bigelow LB. A negative, double-blind, placebo-controlled, clinical trial of verapamil in chronic schizophrenia. Biol Psychiatry 21(7), 691-694 (1986).PubMedCrossRefGoogle Scholar
  89. 89.
    Stedman TJ, Whiteford HA, Eyles D, Welham JL, Pond SM. Effects of nifedipine on psychosis and tardive dyskinesia in schizophrenic patients. J Clin Psychopharmacol 11(1), 43-47 (1991).PubMedCrossRefGoogle Scholar
  90. 90.
    Suddath RL, Straw GM, Freed WJ, Bigelow LB, Kirch DG, Wyatt RJ. A clinical trial of nifedipine in schizophrenia and tardive dyskinesia. Pharmacol Biochem Behav 39(3), 743-745 (1991).PubMedCrossRefGoogle Scholar
  91. 91.
    Kosten TR, Woods SW, Rosen MI, Pearsall HR. Interactions of cocaine with nimodipine: a brief report. Am J Addict 8(1), 77-81 (1999).PubMedCrossRefGoogle Scholar
  92. 92.
    Sofuoglu M, Singha A, Kosten TR, McCance-Katz FE, Petrakis I, Oliveto A. Effects of naltrexone and isradipine, alone or in combination, on cocaine responses in humans. Pharmacol Biochem Behav 75(4), 801-808 (2003).PubMedCrossRefGoogle Scholar
  93. 93.
    Roache JD, Johnson BA, Ait-Daoud N, et al. Effects of repeated-dose isradipine on the abuse liability of cocaine. Exp Clin Psychopharmacol 13(4), 319-326 (2005).PubMedCrossRefGoogle Scholar
  94. 94.
    Rosse RB, Alim TN, Fay-McCarthy M, et al. Nimodipine pharmacotherapeutic adjuvant therapy for inpatient treatment of cocaine dependence. Clin Neuropharmacol 17(4), 348-358 (1994).PubMedCrossRefGoogle Scholar
  95. 95.
    Muntaner C, Kumor KM, Nagoshi C, Jaffe JH. Effects of nifedipine pretreatment on subjective and cardiovascular responses to intravenous cocaine in humans. Psychopharmacology (Berl) 105(1), 37-41 (1991).CrossRefGoogle Scholar
  96. 96.
    Malcolm R, Brady KT, Moore J, Kajdasz D. Amlodipine treatment of cocaine dependence. J Psychoactive Drugs 31(2), 117-120 (1999).PubMedCrossRefGoogle Scholar
  97. 97.
    Johnson BA, Roache JD, Ait-Daoud N, Wells LT, Mauldin JB. Effects of isradipine on cocaine-induced subjective mood. J Clin Psychopharmacol 24(2), 180-191 (2004).PubMedCrossRefGoogle Scholar
  98. 98.
    Vaupel DB, Lange WR, London ED. Effects of verapamil on morphine-induced euphoria, analgesia and respiratory depression in humans. J Pharmacol Exp Ther 267(3), 1386-1394 (1993).PubMedGoogle Scholar
  99. 99.
    Hasegawa AE, Zacny JP. The influence of three L-type calcium channel blockers on morphine effects in healthy volunteers. Anesth Analg 85(3), 633-638 (1997).PubMedCrossRefGoogle Scholar
  100. 100.
    Silverstone PH, Attenburrow MJ, Robson P. The calcium channel antagonist nifedipine causes confusion when used to treat opiate withdrawal in morphine-dependent patients. Int Clin Psychopharmacol 7(2), 87-90 (1992).PubMedGoogle Scholar
  101. 101.
    Zacny JP, Yajnik S. Effects of calcium channel inhibitors on ethanol effects and pharmacokinetics in healthy volunteers. Alcohol 10(6), 505-509 (1993).PubMedCrossRefGoogle Scholar
  102. 102.
    Rush CR, Pazzaglia PJ. Pretreatment with isradipine, a calcium-channel blocker, does not attenuate the acute behavioral effects of ethanol in humans. Alcohol Clin Exp Res 22(2), 539-547 (1998).PubMedCrossRefGoogle Scholar
  103. 103.
    Perez-Reyes M, White WR, Hicks RE. Interaction between ethanol and calcium channel blockers in humans. Alcohol Clin Exp Res 16(4), 769-775 (1992).PubMedCrossRefGoogle Scholar
  104. 104.
    Altamura AC, Regazzetti MG, Porta M. Nimodipine in human alcohol withdrawal syndrome--an open study. Eur Neuropsychopharmacol 1(1), 37-40 (1990).PubMedCrossRefGoogle Scholar
  105. 105.
    Waltereit R, Mannhardt S, Nescholta S, Maser-Gluth C, Bartsch D. Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response. Learn Mem 15(5), 348-356 (2008).PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Busquet P, Hetzenauer A, Sinnegger-Brauns MJ, Striessnig J, Singewald N. Role of L-type Ca2+ channel isoforms in the extinction of conditioned fear. Learn Mem 15(5), 378-386 (2008).PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Bergson P, Lipkind G, Lee SP, Duban ME, Hanck DA. Verapamil block of T-type calcium channels. Mol Pharmacol 79(3), 411-419 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Zhang S, Zhou Z, Gong Q, Makielski JC, January CT. Mechanism of block and identification of the verapamil binding domain to HERG potassium channels. Circ Res 84(9), 989-998 (1999).PubMedCrossRefGoogle Scholar
  109. 109.
    Catacuzzeno L, Trequattrini C, Petris A, Franciolini F. Mechanism of verapamil block of a neuronal delayed rectifier K channel: active form of the blocker and location of its binding domain. Br J Pharmacol 126(8), 1699-1706 (1999).PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Harper AA, Catacuzzeno L, Trequattrini C, Petris A, Franciolini F. Verapamil block of large-conductance Ca-activated K channels in rat aortic myocytes. J Membr Biol 179(2), 103-111 (2001).PubMedCrossRefGoogle Scholar
  111. 111.
    Motulsky HJ, Snavely MD, Hughes RJ, Insel PA. Interaction of verapamil and other calcium channel blockers with alpha 1- and alpha 2-adrenergic receptors. Circ Res 52(2), 226-231 (1983).PubMedCrossRefGoogle Scholar
  112. 112.
    Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther 75(1), 13-33 (2004).PubMedCrossRefGoogle Scholar
  113. 113.
    Pauli-Magnus C, von Richter O, Burk O, et al. Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein. J Pharmacol Exp Ther 293(2), 376-382 (2000).PubMedGoogle Scholar
  114. 114.
    Loscher W, Luna-Tortos C, Romermann K, Fedrowitz M. Do ATP-binding cassette transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which antiepileptic drugs are affected. Curr Pharm Des 17(26), 2808-2828 (2011).PubMedCrossRefGoogle Scholar
  115. 115.
    Raderer M, Scheithauer W. Clinical trials of agents that reverse multidrug resistance. A literature review. Cancer 72(12), 3553-3563 (1993).PubMedCrossRefGoogle Scholar
  116. 116.
    Cipriani A, Saunders K, Attenburrow MJ, et al. A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development. Mol Psychiatry 21(10), 1324-1332 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Casamassima F, Hay AC, Benedetti A, Lattanzi L, Cassano GB, Perlis RH. L-type calcium channels and psychiatric disorders: a brief review. Am J Med Genet B Neuropsychiatr Genet 153B(8), 1373-1390 (2010).PubMedCrossRefGoogle Scholar
  118. 118.
    Deisseroth K, Heist EK, Tsien RW. Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature 392(6672), 198-202 (1998).PubMedCrossRefGoogle Scholar
  119. 119.
    Ma H, Groth RD, Cohen SM, et al. gammaCaMKII shuttles Ca(2)(+)/CaM to the nucleus to trigger CREB phosphorylation and gene expression. Cell 159(2), 281-294 (2014).Google Scholar
  120. 120.
    Wheeler DG, Barrett CF, Groth RD, Safa P, Tsien RW. CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation-transcription coupling. J Cell Biol 183(5), 849-863 (2008).PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Cohen SM, Li B, Tsien RW, Ma H. Evolutionary and functional perspectives on signaling from neuronal surface to nucleus. Biochem Biophys Res Commun 460(1), 88-99 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Ma H, Li B, Tsien RW. Distinct roles of multiple isoforms of CaMKII in signaling to the nucleus. Biochim Biophys Acta 1853(9), 1953-1957 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Wu GY, Deisseroth K, Tsien RW. Activity-dependent CREB phosphorylation: convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway. Proc Natl Acad Sci U S A 98(5), 2808-2813 (2001).PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Wu GY, Deisseroth K, Tsien RW. Spaced stimuli stabilize MAPK pathway activation and its effects on dendritic morphology. Nat Neurosci 4(2), 151-158 (2001).PubMedCrossRefGoogle Scholar
  125. 125.
    Dolmetsch RE, Pajvani U, Fife K, Spotts JM, Greenberg ME. Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway. Science 294(5541), 333-339 (2001).PubMedCrossRefGoogle Scholar
  126. 126.
    Hofmann HA. Functional genomics of neural and behavioral plasticity. J Neurobiol 54(1), 272-282 (2003).PubMedCrossRefGoogle Scholar
  127. 127.
    Ortega-Martinez S. A new perspective on the role of the CREB family of transcription factors in memory consolidation via adult hippocampal neurogenesis. Front Mol Neurosci 8, 46 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Nestler EJ. Cellular basis of memory for addiction. Dialogues Clin Neurosci 15(4), 431-443 (2013).PubMedPubMedCentralGoogle Scholar
  129. 129.
    Harrington AJ, Raissi A, Rajkovich K, et al. MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders. Elife 2016;5:e20059.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Lombardi LM, Baker SA, Zoghbi HY. MECP2 disorders: from the clinic to mice and back. J Clin Invest 125(8), 2914-2923 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Mao Z, Bonni A, Xia F, Nadal-Vicens M, Greenberg ME. Neuronal activity-dependent cell survival mediated by transcription factor MEF2. Science 286(5440), 785-790 (1999).PubMedCrossRefGoogle Scholar
  132. 132.
    Tian Y, Voineagu I, Pasca SP, et al. Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome. Genome Med 6(10), 75 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Chen WG, Chang Q, Lin Y, et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302(5646), 885-889 (2003).PubMedCrossRefGoogle Scholar
  134. 134.
    Pfeiffer BE, Zang T, Wilkerson JR, et al. Fragile X mental retardation protein is required for synapse elimination by the activity-dependent transcription factor MEF2. Neuron 66(2), 191-197 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Murphy JG, Sanderson JL, Gorski JA, et al. AKAP-anchored PKA maintains neuronal L-type calcium channel activity and NFAT transcriptional signaling. Cell Rep 7(5), 1577-1588 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Graef IA, Mermelstein PG, Stankunas K, et al. L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons. Nature 401(6754), 703-708 (1999).PubMedCrossRefGoogle Scholar
  137. 137.
    Nurnberger JI, Jr., Koller DL, Jung J, et al. Identification of pathways for bipolar disorder: a meta-analysis. JAMA Psychiatry 71(6), 657-664 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Darby MM, Yolken RH, Sabunciyan S. Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders. Transl Psychiatry 6(9), e890 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Hertzberg L, Katsel P, Roussos P, Haroutunian V, Domany E. Integration of gene expression and GWAS results supports involvement of calcium signaling in Schizophrenia. Schizophr Res, 164(1-3), 92-99 (2015).PubMedCrossRefGoogle Scholar
  140. 140.
    Wen Y, Alshikho MJ, Herbert MR. Pathway network analyses for autism reveal multisystem involvement, major overlaps with other diseases and convergence upon MAPK and calcium signaling. PLOS ONE 11(4), e0153329 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Focking M, Lopez LM, English JA, et al. Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia. Mol Psychiatry 20(4), 424-432 (2015).PubMedCrossRefGoogle Scholar
  142. 142.
    Focking M, Dicker P, Lopez LM, et al. Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder. Transl Psychiatry 6(11), e959 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Pinto D, Delaby E, Merico D, et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet 94(5), 677-694 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Nho K, Ramanan VK, Horgusluoglu E, et al. Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults. J Alzheimers Dis 45(4), 1197-1206 (2015).PubMedPubMedCentralGoogle Scholar
  145. 145.
    Kerner B, Rao AR, Christensen B, Dandekar S, Yourshaw M, Nelson SF. Rare genomic variants link bipolar disorder with anxiety disorders to CREB-regulated intracellular signaling pathways. Front Psychiatry 4, 154 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Wek RC, Cavener DR. Translational control and the unfolded protein response. Antioxid Redox Signal 9(12), 2357-2371 (2007).PubMedCrossRefGoogle Scholar
  147. 147.
    Krey JF, Paşca SP, Shcheglovitov A, et al. Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. Nat Neurosci 16(2), 201-209 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Pasca SP, Portmann T, Voineagu I, et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med 17(12), 1657-1662 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Lee AS, De Jesus-Cortes H, Kabir ZD, et al. The neuropsychiatric disease-associated gene cacna1c mediates survival of young hippocampal neurons. eNeuro 3(2) (2016).Google Scholar
  150. 150.
    Kabir ZD, Che A, D F et al. Rescue of impaired sociability and anxietylike behavior in adult cacna1cdeficient mice by pharmacologically targeting eIF2α. Molecular Psychiatry (2017, in press).Google Scholar
  151. 151.
    Mullins C, Fishell G, Tsien RW. Unifying views of autism spectrum disorders: a consideration of autoregulatory feedback loops. Neuron 89(6), 1131-1156 (2016).PubMedCrossRefGoogle Scholar
  152. 152.
    Kabir ZD, Lee AS, Burgdorf CE, et al. Cacna1c in the prefrontal cortex regulates depression-related behaviors via REDD1. Neuropsychopharmacology 2017 Jan 4 [Epub ahead of print].Google Scholar
  153. 153.
    Lee AS, Ra S, Rajadhyaksha AM, et al. Forebrain elimination of cacna1c mediates anxiety-like behavior in mice. Mol Psychiatry 17(11), 1054-1055 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Hess P, Lansman JB, Tsien RW. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature 311(5986), 538-544 (1984).PubMedCrossRefGoogle Scholar
  155. 155.
    Seisenberger C, Specht V, Welling A et al. Functional embryonic cardiomyocytes after disruption of the L-type alpha1C (Cav1.2) calcium channel gene in the mouse. J Biol Chem 275(50), 39193-39199 (2000).PubMedCrossRefGoogle Scholar
  156. 156.
    Goonasekera SA, Hammer K, Auger-Messier M, et al. Decreased cardiac L-type Ca(2)(+) channel activity induces hypertrophy and heart failure in mice. J Clin Invest 122(1), 280-290 (2012).PubMedCrossRefGoogle Scholar
  157. 157.
    Dao DT, Mahon PB, Cai X, et al. Mood disorder susceptibility gene CACNA1C modifies mood-related behaviors in mice and interacts with sex to influence behavior in mice and diagnosis in humans. Biol Psychiatry 68(9), 801-810 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Bavley CC, Fischer DK, Rizzo BK, Rajadhyaksha AM. Cav1.2 channels mediate persistent chronic stress-induced behavioral deficits that are associated with prefrontal cortex activation of the p25/Cdk5-glucocorticoid receptor pathway. Neurobiol Stress 7, 27-37 (2017).PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Sinnegger-Brauns MJ, Hetzenauer A, Huber IG, et al. Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels. J Clin Invest 113(10), 1430-1439 (2004).PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Giordano TP, Tropea TF, Satpute SS, et al. Molecular switch from L-type Ca v 1.3 to Ca v 1.2 Ca2+ channel signaling underlies long-term psychostimulant-induced behavioral and molecular plasticity. J Neurosci 30(50), 17051-17062 (2010).Google Scholar
  161. 161.
    Schierberl K, Hao J, Tropea TF, et al. Cav1.2 L-type Ca(2)(+) channels mediate cocaine-induced GluA1 trafficking in the nucleus accumbens, a long-term adaptation dependent on ventral tegmental area Ca(v)1.3 channels. J Neurosci 31(38), 13562-13575 (2011).Google Scholar
  162. 162.
    Kessler RC, Aguilar-Gaxiola S, Alonso J, et al. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc 18(1), 23-33 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Erk S, Meyer-Lindenberg A, Linden DE, et al. Replication of brain function effects of a genome-wide supported psychiatric risk variant in the CACNA1C gene and new multi-locus effects. Neuroimage 94, 147-154 (2014).PubMedCrossRefGoogle Scholar
  164. 164.
    Erk S, Meyer-Lindenberg A, Schnell K, et al. Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch Gen Psychiatry 67(8), 803-811 (2010).PubMedCrossRefGoogle Scholar
  165. 165.
    Roussos P, Giakoumaki SG, Georgakopoulos A, Robakis NK, Bitsios P. The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males. Bipolar Disord 13(3), 250-259 (2011).PubMedCrossRefGoogle Scholar
  166. 166.
    Wang F, McIntosh AM, He Y, Gelernter J, Blumberg HP. The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disord 13(7-8), 696-700 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Dima D, Jogia J, Collier D, Vassos E, Burdick KE, Frangou S. Independent modulation of engagement and connectivity of the facial network during affect processing by CACNA1C and ANK3 risk genes for bipolar disorder. JAMA Psychiatry 70(12), 1303-1311 (2013).PubMedCrossRefGoogle Scholar
  168. 168.
    Bader PL, Faizi M, Kim LH, et al. Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci U S A 108(37), 15432-15437 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Kennedy DP, Adolphs R. The social brain in psychiatric and neurological disorders. Trends Cogn Sci 16(11), 559-572 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.), (2013). Arlington, VA: American Psychiatric Association.Google Scholar
  171. 171.
    Grant BF, Hasin DS, Blanco C, et al. The epidemiology of social anxiety disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 66(11), 1351-1361 (2005).PubMedCrossRefGoogle Scholar
  172. 172.
    Hidalgo RB, Barnett SD, Davidson JR. Social anxiety disorder in review: two decades of progress. Int J Neuropsychopharmacol 4(3), 279-298 (2001).PubMedCrossRefGoogle Scholar
  173. 173.
    Allsop SA, Vander Weele CM, Wichmann R, Tye KM. Optogenetic insights on the relationship between anxiety-related behaviors and social deficits. Front Behav Neurosci 8, 241 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Workman ER, Niere F, Raab-Graham KF. mTORC1-dependent protein synthesis underlying rapid antidepressant effect requires GABABR signaling. Neuropharmacology 73, 192-203 (2013).PubMedCrossRefGoogle Scholar
  175. 175.
    Nandagopal N, Roux PP. Regulation of global and specific mRNA translation by the mTOR signaling pathway. Translation 3(1), e983402 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Costa-Mattioli M, Monteggia LM. mTOR complexes in neurodevelopmental and neuropsychiatric disorders. Nat Neurosci 16(11), 1537-1543 (2013).PubMedCrossRefGoogle Scholar
  177. 177.
    Gkogkas CG, Khoutorsky A, Ran I, et al. Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 493(7432), 371-377 (2013).PubMedCrossRefGoogle Scholar
  178. 178.
    Santini E, Huynh TN, MacAskill AF, et al. Exaggerated translation causes synaptic and behavioural aberrations associated with autism. Nature 493(7432), 411-415 (2013).PubMedCrossRefGoogle Scholar
  179. 179.
    Sato A, Kasai S, Kobayashi T, et al. Rapamycin reverses impaired social interaction in mouse models of tuberous sclerosis complex. Nat Commun 3, 1292 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Hwang SK, Lee JH, Yang JE, et al. Everolimus improves neuropsychiatric symptoms in a patient with tuberous sclerosis carrying a novel TSC2 mutation. Mol Brain 9(1), 56 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Ricciardi S, Boggio EM, Grosso S, et al. Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model. Hum Mol Genet 20(6), 1182-1196 (2011).PubMedCrossRefGoogle Scholar
  182. 182.
    Sidrauski C, McGeachy AM, Ingolia NT, Walter P. The small molecule ISRIB reverses the effects of eIF2alpha phosphorylation on translation and stress granule assembly. Elife 4 (2015).Google Scholar
  183. 183.
    Zimmerman HR, Beckelman B, Yang W, Ma T. Interactions between the eIF2a and mTORC1 signaling pathways. Program No. 126.02. 2016 Neuroscience Meeting Planner, San Diego, Society for Neuroscience, Online (2016).Google Scholar
  184. 184.
    Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2, e00498 (2013).Google Scholar
  185. 185.
    Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis. Gene 273(1), 1-11 (2001).PubMedCrossRefGoogle Scholar
  186. 186.
    Mogilnicka E, Czyrak A, Maj J. Dihydropyridine calcium channel antagonists reduce immobility in the mouse behavioral despair test; antidepressants facilitate nifedipine action. Eur J Pharmacol 138(3), 413-416 (1987).PubMedCrossRefGoogle Scholar
  187. 187.
    Cohen C, Perrault G, Sanger DJ. Assessment of the antidepressant-like effects of L-type voltage-dependent channel modulators. Behav Pharmacol 8(6-7), 629-638 (1997).PubMedCrossRefGoogle Scholar
  188. 188.
    Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329(5994), 959-964 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Mogilnicka E, Czyrak A, Maj J. BAY K 8644 enhances immobility in the mouse behavioral despair test, an effect blocked by nifedipine. Eur J Pharmacol 151(2), 307-311 (1988).PubMedCrossRefGoogle Scholar
  190. 190.
    Ota KT, Liu RJ, Voleti B, et al. REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nat Med 20(5), 531-535 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Magno LA, Santana CV, Sacramento EK, et al. Genetic variations in FOXO3A are associated with Bipolar Disorder without confering vulnerability for suicidal behavior. J Affect Disord 133(3), 633-637 (2011).PubMedCrossRefGoogle Scholar
  192. 192.
    Wang H, Quirion R, Little PJ, et al. Forkhead box O transcription factors as possible mediators in the development of major depression. Neuropharmacology 99, 527-537 (2015).PubMedCrossRefGoogle Scholar
  193. 193.
    Polter A, Yang S, Zmijewska AA et al. Forkhead box, class O transcription factors in brain: regulation and behavioral manifestation. Biol Psychiatry 65(2), 150-159 (2009).PubMedCrossRefGoogle Scholar
  194. 194.
    Mao Z, Liu L, Zhang R, Li X. Lithium reduces FoxO3a transcriptional activity by decreasing its intracellular content. Biol Psychiatry 62(12), 1423-1430 (2007).PubMedCrossRefGoogle Scholar
  195. 195.
    Millan MJ, Agid Y, Brune M, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 11(2), 141-168 (2012).PubMedCrossRefGoogle Scholar
  196. 196.
    White JA, McKinney BC, John MC, Powers PA, Kamp TJ, Murphy GG. Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice. Learn Mem 15(1), 1-5 (2008).PubMedCrossRefGoogle Scholar
  197. 197.
    Temme SJ, Bell RZ, Fisher GL, Murphy GG. Deletion of the mouse homolog of CACNA1C disrupts discrete forms of hippocampal-dependent memory and neurogenesis within the dentate gyrus. eNeuro, 3(6) (2016).Google Scholar
  198. 198.
    Moosmang S, Haider N, Klugbauer N, et al. Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. J Neurosci 25(43), 9883-9892 (2005).PubMedCrossRefGoogle Scholar
  199. 199.
    Nicoll RA. A brief history of long-term potentiation. Neuron 93(2), 281-290 (2017).PubMedCrossRefGoogle Scholar
  200. 200.
    Yau SY, Li A, So KF. Involvement of adult hippocampal neurogenesis in learning and forgetting. Neural Plast 2015, 717958 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11(5), 339-350 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Waltz JA. The neural underpinnings of cognitive flexibility and their disruption in psychotic illness. Neuroscience 345, 203-217 (2017).PubMedCrossRefGoogle Scholar
  203. 203.
    LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci 23, 155-184 (2000).PubMedCrossRefGoogle Scholar
  204. 204.
    Pezze MA, Feldon J. Mesolimbic dopaminergic pathways in fear conditioning. Prog Neurobiol 74(5), 301-320 (2004).PubMedCrossRefGoogle Scholar
  205. 205.
    Singewald N, Schmuckermair C, Whittle N, Holmes A, Ressler KJ. Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders. Pharmacol Ther 149, 150-190 (2015).PubMedCrossRefGoogle Scholar
  206. 206.
    Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry 54(5), 504-514 (2003).PubMedCrossRefGoogle Scholar
  207. 207.
    Cain CK, Blouin AM, Barad M. L-type voltage-gated calcium channels are required for extinction, but not for acquisition or expression, of conditional fear in mice. J Neurosci 22(20), 9113-9121 (2002).PubMedGoogle Scholar
  208. 208.
    Bauer EP, Schafe GE, LeDoux JE. NMDA receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala. J Neurosci 22(12), 5239-5249 (2002).PubMedGoogle Scholar
  209. 209.
    Davis SE, Bauer EP. L-type voltage-gated calcium channels in the basolateral amygdala are necessary for fear extinction. J Neurosci 32(39), 13582-13586 (2012).PubMedCrossRefGoogle Scholar
  210. 210.
    Langwieser N, Christel CJ, Kleppisch T, Hofmann F, Wotjak CT, Moosmang S. Homeostatic switch in hebbian plasticity and fear learning after sustained loss of Cav1.2 calcium channels. J Neurosci 30(25), 8367-8375 (2010).Google Scholar
  211. 211.
    McKinney BC, Sze W, White JA, Murphy GG. L-type voltage-gated calcium channels in conditioned fear: a genetic and pharmacological analysis. Learn Mem 15(5), 326-334 (2008).PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    Barad M, Blouin AM, Cain CK. Like extinction, latent inhibition of conditioned fear in mice is blocked by systemic inhibition of L-type voltage-gated calcium channels. Learn Mem 11(5), 536-539 (2004).PubMedCrossRefGoogle Scholar
  213. 213.
    Shinnick-Gallagher P, McKernan MG, Xie J, Zinebi F. L-type voltage-gated calcium channels are involved in the in vivo and in vitro expression of fear conditioning. Ann N Y Acad Sci 985, 135-149 (2003).PubMedCrossRefGoogle Scholar
  214. 214.
    Weisskopf MG, Bauer EP, LeDoux JE. L-type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala. J Neurosci 19(23), 10512-10519 (1999).PubMedGoogle Scholar
  215. 215.
    Lee O, Lee CJ, Choi S. Induction mechanisms for L-LTP at thalamic input synapses to the lateral amygdala: requirement of mGluR5 activation. Neuroreport 13(5), 685-691 (2002).PubMedCrossRefGoogle Scholar
  216. 216.
    Pape HC, Pare D. Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 90(2), 419-463 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  217. 217.
    Meis S, Endres T, Lessmann V. Postsynaptic BDNF signalling regulates long-term potentiation at thalamo-amygdala afferents. J Physiol 590(1), 193-208 (2012).PubMedCrossRefGoogle Scholar
  218. 218.
    Ghosh A, Carnahan J, Greenberg ME. Requirement for BDNF in activity-dependent survival of cortical neurons. Science 263(5153), 1618-1623 (1994).PubMedCrossRefGoogle Scholar
  219. 219.
    Rattiner LM, Davis M, French CT, Ressler KJ. Brain-derived neurotrophic factor and tyrosine kinase receptor B involvement in amygdala-dependent fear conditioning. J Neurosci 24(20), 4796-4806 (2004).PubMedCrossRefGoogle Scholar
  220. 220.
    Ou LC, Gean PW. Transcriptional regulation of brain-derived neurotrophic factor in the amygdala during consolidation of fear memory. Mol Pharmacol 72(2), 350-358 (2007).PubMedCrossRefGoogle Scholar
  221. 221.
    See V, Boutillier AL, Bito H, Loeffler JP. Calcium/calmodulin-dependent protein kinase type IV (CaMKIV) inhibits apoptosis induced by potassium deprivation in cerebellar granule neurons. FASEB J 15(1), 134-144 (2001).PubMedCrossRefGoogle Scholar
  222. 222.
    Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME. Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20(4), 709-726 (1998).PubMedCrossRefGoogle Scholar
  223. 223.
    Pieper AA, Wu X, Han TW, et al. The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice. Proc Natl Acad Sci U S A 102(39), 14052-14057 (2005).PubMedPubMedCentralCrossRefGoogle Scholar
  224. 224.
    Pickard BS, Pieper AA, Porteous DJ, Blackwood DH, Muir WJ. The NPAS3 gene—emerging evidence for a role in psychiatric illness. Ann Med 38(6), 439-448 (2006).PubMedCrossRefGoogle Scholar
  225. 225.
    Reif A, Schmitt A, Fritzen S, Lesch KP. Neurogenesis and schizophrenia: dividing neurons in a divided mind? Eur Arch Psychiatry Clin Neurosci 257(5), 290-299 (2007).PubMedCrossRefGoogle Scholar
  226. 226.
    Pickard B. Progress in defining the biological causes of schizophrenia. Exp Rev Mol Med 13, e25 (2011).CrossRefGoogle Scholar
  227. 227.
    Wu Q, Li Y, Xiao B. DISC1-related signaling pathways in adult neurogenesis of the hippocampus. Gene 518(2), 223-230 (2013).PubMedCrossRefGoogle Scholar
  228. 228.
    Schreiber R, Newman-Tancredi A. Improving cognition in schizophrenia with antipsychotics that elicit neurogenesis through 5-HT(1A) receptor activation. Neurobiol Learn Mem 110, 72-80 (2014).PubMedCrossRefGoogle Scholar
  229. 229.
    Ohira K, Kobayashi K, Toyama K, et al. Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice. Mol Brain 6, 12 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Le Strat Y, Ramoz N, Gorwood P. The role of genes involved in neuroplasticity and neurogenesis in the observation of a gene-environment interaction (GxE) in schizophrenia. Curr Mol Med 9(4), 506-518 (2009).PubMedCrossRefGoogle Scholar
  231. 231.
    Knight HM, Walker R, James R, et al. GRIK4/KA1 protein expression in human brain and correlation with bipolar disorder risk variant status. Am J Med Genet B Neuropsychiatr Genet 159B(1), 21-29 (2012).PubMedCrossRefGoogle Scholar
  232. 232.
    Serafini G, Hayley S, Pompili M, et al. Hippocampal neurogenesis, neurotrophic factors and depression: possible therapeutic targets? CNS Neurol Disord Drug Targets 13(10), 1708-1721 (2014).PubMedCrossRefGoogle Scholar
  233. 233.
    Walker AK, Rivera PD, Wang Q, et al. The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis. Mol Psychiatry 20(4), 500-508 (2015).PubMedCrossRefGoogle Scholar
  234. 234.
    Amiri A, Cho W, Zhou J, et al. Pten deletion in adult hippocampal neural stem/progenitor cells causes cellular abnormalities and alters neurogenesis. J Neurosci 32(17), 5880-5890 (2012).PubMedCrossRefGoogle Scholar
  235. 235.
    Jolly LA, Homan CC, Jacob R, Barry S, Gecz J. The UPF3B gene, implicated in intellectual disability, autism, ADHD and childhood onset schizophrenia regulates neural progenitor cell behaviour and neuronal outgrowth. Hum Mol Genet 22(23), 4673-4687 (2013).PubMedCrossRefGoogle Scholar
  236. 236.
    Cope EC, Briones BA, Brockett AT, et al. Immature neurons and radial glia, but not astrocytes or microglia, are altered in adult Cntnap2 and Shank3 mice, models of autism. eNeuro, 3(5) (2016).Google Scholar
  237. 237.
    Chen Z, Li X, Zhou J, et al. Accumulated quiescent neural stem cells in adult hippocampus of the mouse model for the MECP2 duplication syndrome. Sci Rep 7, 41701 (2017).PubMedPubMedCentralCrossRefGoogle Scholar
  238. 238.
    Dabe EC, Majdak P, Bhattacharya TK, Miller DS, Rhodes JS. Chronic D-amphetamine administered from childhood to adulthood dose-dependently increases the survival of new neurons in the hippocampus of male C57BL/6J mice. Neuroscience 231, 125-135 (2013).PubMedCrossRefGoogle Scholar
  239. 239.
    Sahay A, Scobie KN, Hill AS, et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472(7344), 466-470 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Hill AS, Sahay A, Hen R. Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology 40(10), 2368-2378 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  241. 241.
    Deisseroth K, Singla S, Toda H, Monje M, Palmer TD, Malenka RC. Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron 42(4), 535-552 (2004).PubMedCrossRefGoogle Scholar
  242. 242.
    Teh DB, Ishizuka T, Yawo H. Regulation of later neurogenic stages of adult-derived neural stem/progenitor cells by L-type Ca2+ channels. Dev Growth Differ 56(8), 583-594 (2014).PubMedCrossRefGoogle Scholar
  243. 243.
    Pieper AA, Xie S, Capota E, et al. Discovery of a proneurogenic, neuroprotective chemical. Cell 142(1), 39-51 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Marschallinger J, Sah A, Schmuckermair C, et al. The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions. Cell Calcium 58(6), 606-616 (2015).Google Scholar
  245. 245.
    Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59(12), 1116-1127 (2006).PubMedCrossRefGoogle Scholar
  246. 246.
    Hill JL, Martinowich K. Activity-dependent signaling: influence on plasticity in circuits controlling fear-related behavior. Curr Opin Neurobiol 36, 59-65 (2016).PubMedCrossRefGoogle Scholar
  247. 247.
    Martinowich K, Manji H, Lu B. New insights into BDNF function in depression and anxiety. Nat Neurosci 10(9), 1089-1093 (2007).PubMedCrossRefGoogle Scholar
  248. 248.
    Lu B, Martinowich K. Cell biology of BDNF and its relevance to schizophrenia. Novartis Foundation symposium, 289, 119-129; discussion 129-135, 193-115 (2008).Google Scholar
  249. 249.
    Zheng F, Zhou X, Luo Y, Xiao H, Wayman G, Wang H. Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons. PLOS ONE 6(12), e28441 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  250. 250.
    Smrt RD, Eaves-Egenes J, Barkho BZ, et al. Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol Dis 27(1), 77-89 (2007).PubMedPubMedCentralCrossRefGoogle Scholar
  251. 251.
    Li H, Zhong X, Chau KF, et al. Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway. Nat Commun 5, 5601 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  252. 252.
    Chen WG, West AE, Tao X, et al. Upstream stimulatory factors are mediators of Ca2+-responsive transcription in neurons. J Neurosci 23(7), 2572-2581 (2003).PubMedGoogle Scholar
  253. 253.
    Tao J, Hu K, Chang Q, et al. Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proc Natl Acad Sci U S A 106(12), 4882-4887 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  254. 254.
    Tao X, West AE, Chen WG, Corfas G, Greenberg ME. A calcium-responsive transcription factor, CaRF, that regulates neuronal activity-dependent expression of BDNF. Neuron 33(3), 383-395 (2002).PubMedCrossRefGoogle Scholar
  255. 255.
    Chao HT, Zoghbi HY. The yin and yang of MeCP2 phosphorylation. Proc Natl Acad Sci U S A 106(12), 4577-4578 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  256. 256.
    Cunha C, Brambilla R, Thomas KL. A simple role for BDNF in learning and memory? Front Mol Neurosci 3, 1 (2010).PubMedPubMedCentralGoogle Scholar
  257. 257.
    Castren E, Kojima M. Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiol Dis 97(Pt B), 119-126 (2017).Google Scholar
  258. 258.
    Kemp SW, Szynkaruk M, Stanoulis KN, et al. Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury. Neuroscience 284, 202-216 (2015).PubMedCrossRefGoogle Scholar
  259. 259.
    Tesla R, Wolf HP, Xu P, et al. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 109(42), 17016-17021 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  260. 260.
    De Jesus-Cortes H, Xu P, Drawbridge J et al. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease. Proc Natl Acad Sci U S A 109(42), 17010-17015 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  261. 261.
    Blaya MO, Bramlett HM, Naidoo J, Pieper AA, Dietrich WD. Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury. J Neurotrauma 31(5), 476-486 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  262. 262.
    Yin TC, Britt JK, De Jesus-Cortes H, et al. P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury. Cell Rep 8(6), 1731-1740 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  263. 263.
    Dutca LM, Stasheff SF, Hedberg-Buenz A, et al. Early detection of subclinical visual damage after blast-mediated TBI enables prevention of chronic visual deficit by treatment with P7C3-S243. Invest Ophthalmol Vis Sci 55(12), 8330-8341 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  264. 264.
    De Jesus-Cortes H, Miller AD, Britt JK, et al. Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson's disease. NPJ Parkinsons Dis 1 (2015).Google Scholar
  265. 265.
    Naidoo J, De Jesus-Cortes H, Huntington P, et al. Discovery of a neuroprotective chemical, (S)-N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties. J Med Chem 57(9), 3746-3754 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  266. 266.
    Pieper AA, McKnight SL, Ready JM. P7C3 and an unbiased approach to drug discovery for neurodegenerative diseases. Chem Soc Rev 43(19), 6716-6726 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  267. 267.
    Gao R, Penzes P. Common mechanisms of excitatory and inhibitory imbalance in schizophrenia and autism spectrum disorders. Curr Mol Med 15(2), 146-167 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  268. 268.
    Bicks LK, Koike H, Akbarian S, Morishita H. Prefrontal cortex and social cognition in mouse and man. Front Psychol 6, 1805 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  269. 269.
    Nelson SB, Valakh V. Excitatory/inhibitory balance and circuit homeostasis in autism spectrum disorders. Neuron 87(4), 684-698 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  270. 270.
    Frank CA. How voltage-gated calcium channels gate forms of homeostatic synaptic plasticity. Front Cell Neurosci 8, 40 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  271. 271.
    Gong B, Wang H, Gu S, Heximer SP, Zhuo M. Genetic evidence for the requirement of adenylyl cyclase 1 in synaptic scaling of forebrain cortical neurons. Eur J Neurosci 26(2), 275-288 (2007).PubMedCrossRefGoogle Scholar
  272. 272.
    Saliba RS, Gu Z, Yan Z, Moss SJ. Blocking L-type voltage-gated Ca2+ channels with dihydropyridines reduces gamma-aminobutyric acid type A receptor expression and synaptic inhibition. J Biol Chem 284(47), 32544-32550 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  273. 273.
    Hirtz JJ, Braun N, Griesemer D, et al. Synaptic refinement of an inhibitory topographic map in the auditory brainstem requires functional Cav1.3 calcium channels. J Neurosci 32(42), 14602-14616 (2012).PubMedCrossRefGoogle Scholar
  274. 274.
    Busquet P, Nguyen NK, Schmid E, et al. CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype. Int J Neuropsychopharmacol 13(4), 499-513 (2010).PubMedCrossRefGoogle Scholar
  275. 275.
    Platzer J, Engel J, Schrott-Fischer A, et al. Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102(1), 89-97 (2000).PubMedCrossRefGoogle Scholar
  276. 276.
    McKinney BC, Murphy GG. The L-Type voltage-gated calcium channel Cav1.3 mediates consolidation, but not extinction, of contextually conditioned fear in mice. Learn Mem 13(5), 584-589 (2006).Google Scholar
  277. 277.
    McKinney BC, Sze W, Lee B, Murphy GG. Impaired long-term potentiation and enhanced neuronal excitability in the amygdala of Ca(V)1.3 knockout mice. Neurobiol Learn Mem 92(4), 519-528 (2009).Google Scholar
  278. 278.
    Hell JW, Westenbroek RE, Warner C, et al. Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits. J Cell Biol 123(4), 949-962 (1993).PubMedCrossRefGoogle Scholar
  279. 279.
    Lancaster TM, Heerey EA, Mantripragada K, Linden DE. CACNA1C risk variant affects reward responsiveness in healthy individuals. Transl Psychiatry 4, e461 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  280. 280.
    Pedram P, Zhai G, Gulliver W, Zhang H, Sun G. Two novel candidate genes identified in adults from the Newfoundland population with addictive tendencies towards food. Appetite 2017 Jan 20 [Epub ahead of print].Google Scholar
  281. 281.
    Bardo MT, Bevins RA. Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl) 153(1), 31-43 (2000).CrossRefGoogle Scholar
  282. 282.
    Degoulet M, Stelly CE, Ahn KC, Morikawa H. L-type Ca(2)(+) channel blockade with antihypertensive medication disrupts VTA synaptic plasticity and drug-associated contextual memory. Mol Psychiatry 21(3), 394-402 (2016).PubMedCrossRefGoogle Scholar
  283. 283.
    Reimer AR, Martin-Iverson MT. Nimodipine and haloperidol attenuate behavioural sensitization to cocaine but only nimodipine blocks the establishment of conditioned locomotion induced by cocaine. Psychopharmacology (Berl) 113(3-4), 404-410 (1994).CrossRefGoogle Scholar
  284. 284.
    Pierce RC, Quick EA, Reeder DC, Morgan ZR, Kalivas PW. Calcium-mediated second messengers modulate the expression of behavioral sensitization to cocaine. J Pharmacol Exp Ther 286(3), 1171-1176 (1998).PubMedGoogle Scholar
  285. 285.
    Pani L, Kuzmin A, Martellotta MC, Gessa GL, Fratta W. The calcium antagonist PN 200-110 inhibits the reinforcing properties of cocaine. Brain Res Bull 26(3), 445-447 (1991).PubMedCrossRefGoogle Scholar
  286. 286.
    Biala G, Langwinski R. Effects of calcium channel antagonists on the reinforcing properties of morphine, ethanol and cocaine as measured by place conditioning. J Physiol Pharmacol 47(3), 497-502 (1996).PubMedGoogle Scholar
  287. 287.
    Shibasaki M, Kurokawa K, Ohkuma S. Upregulation of L-type Ca(v)1 channels in the development of psychological dependence. Synapse 64(6), 440-444 (2010).PubMedCrossRefGoogle Scholar
  288. 288.
    Kuzmin A, Zvartau E, Gessa GL, Martellotta MC, Fratta W. Calcium antagonists isradipine and nimodipine suppress cocaine and morphine intravenous self-administration in drug-naive mice. Pharmacol Biochem Behav 41(3), 497-500 (1992).PubMedCrossRefGoogle Scholar
  289. 289.
    Anderson SM, Famous KR, Sadri-Vakili G, et al. CaMKII: a biochemical bridge linking accumbens dopamine and glutamate systems in cocaine seeking. Nat Neurosci 11(3), 344-353 (2008).PubMedCrossRefGoogle Scholar
  290. 290.
    Zhang Q, Li J-X, Zheng J-W, Liu R-K, Liang J-H. L-type Ca2+ channel blockers inhibit the development but not the expression of sensitization to morphine in mice. Eur J Pharmacol 467(1-3), 145-150 (2003).PubMedCrossRefGoogle Scholar
  291. 291.
    Kuzmin A, Patkina N, Pchelintsev M, Zvartau E. Isradipine is able to separate morphine-induced analgesia and place conditioning. Brain Res 593(2), 221-225 (1992).PubMedCrossRefGoogle Scholar
  292. 292.
    Michaluk J, Karolewicz B, Antkiewicz-Michaluk L, Vetulani J. Effects of various Ca2+ channel antagonists on morphine analgesia, tolerance and dependence, and on blood pressure in the rat. Eur J Pharmacol, 352(2-3), 189-197 (1998).PubMedCrossRefGoogle Scholar
  293. 293.
    Tokuyama S, Feng Y, Wakabayashi H, Ho IK. Ca2+ channel blocker, diltiazem, prevents physical dependence and the enhancement of protein kinase C activity by opioid infusion in rats. Eur J Pharmacol 279(1), 93-98 (1995).PubMedCrossRefGoogle Scholar
  294. 294.
    Tokuyama S, Ho IK. Inhibitory effects of diltiazem, an L-type Ca2+ channel blocker, on naloxone-increased glutamate levels in the locus coeruleus of opioid-dependent rats. Brain Res 722(1-2), 212-216 (1996).PubMedCrossRefGoogle Scholar
  295. 295.
    Baeyens JM, Esposito E, Ossowska G, Samanin R. Effects of peripheral and central administration of calcium channel blockers in the naloxone-precipitated abstinence syndrome in morphine-dependent rats. Eur J Pharmacol 137(1), 9-13 (1987).PubMedCrossRefGoogle Scholar
  296. 296.
    Bongianni F, Carla V, Moroni F, Pellegrini-Giampietro DE. Calcium channel inhibitors suppress the morphine-withdrawal syndrome in rats. Br J Pharmacol 88(3), 561-567 (1986).PubMedPubMedCentralCrossRefGoogle Scholar
  297. 297.
    Barrios M, Baeyens JM. Differential effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine. Psychopharmacology (Berl) 104(3), 397-403 (1991).CrossRefGoogle Scholar
  298. 298.
    Zharkovsky A, Totterman AM, Moisio J, Ahtee L. Concurrent nimodipine attenuates the withdrawal signs and the increase of cerebral dihydropyridine binding after chronic morphine treatment in rats. Naunyn Schmiedebergs Arch Pharmacol 347(5), 483-486 (1993).PubMedCrossRefGoogle Scholar
  299. 299.
    Vaseghi G, Rabbani M, Hajhashemi V. The effect of nimodipine on memory impairment during spontaneous morphine withdrawal in mice: Corticosterone interaction. Eur J Pharmacol 695(1-3), 83-87 (2012).PubMedCrossRefGoogle Scholar
  300. 300.
    Vitcheva V, Mitcheva M. Effects of nifedipine on behavioral and biochemical parameters in rats after multiple morphine administration. Methods Find Exp Clin Pharmacol 26(8), 631-634 (2004).PubMedCrossRefGoogle Scholar
  301. 301.
    Engel JA, Fahlke C, Hulthe P, et al. Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists. J Neural Transm 74(3), 181-193 (1988).PubMedCrossRefGoogle Scholar
  302. 302.
    Rezvani AH, Janowsky DS. Decreased alcohol consumption by verapamil in alcohol preferring rats. Prog Neuropsychopharmacol Biol Psychiatry 14(4), 623-631 (1990).PubMedCrossRefGoogle Scholar
  303. 303.
    Fadda F, Garau B, Colombo G, Gessa GL. Isradipine and other calcium channel antagonists attenuate ethanol consumption in ethanol-preferring rats. Alcohol Clin Exp Res 16(3), 449-452 (1992).PubMedCrossRefGoogle Scholar
  304. 304.
    De Beun R, Schneider R, Klein A, Lohmann A, De Vry J. Effects of nimodipine and other calcium channel antagonists in alcohol-preferring AA rats. Alcohol 13(3), 263-271 (1996).PubMedCrossRefGoogle Scholar
  305. 305.
    Green-Jordan K, Grant KA. Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats. Psychopharmacology (Berl) 149(1), 84-92 (2000).CrossRefGoogle Scholar
  306. 306.
    Holt JD, Watson WP, Little HJ. Studies on a model of long term alcohol drinking. Behav Brain Res 123(2), 193-200 (2001).PubMedCrossRefGoogle Scholar
  307. 307.
    Balino P, Pastor R, Aragon CM. Participation of L-type calcium channels in ethanol-induced behavioral stimulation and motor incoordination: effects of diltiazem and verapamil. Behav Brain Res 209(2), 196-204 (2010).PubMedCrossRefGoogle Scholar
  308. 308.
    White JM, Smith AM. Modification of the behavioural effects of ethanol by nifedipine. Alcohol Alcohol 27(2), 137-141 (1992).PubMedGoogle Scholar
  309. 309.
    Czarnecka E, Kubik-Bogucka E. Effects of calcium antagonists on central actions of ethanol: comparative studies with nifedipine, verapamil and cinnarizine. Alcohol Alcohol 28(6), 649-655 (1993).PubMedGoogle Scholar
  310. 310.
    Whittington MA, Dolin SJ, Patch TL, Siarey RJ, Butterworth AR, Little HJ. Chronic dihydropyridine treatment can reverse the behavioural consequences of and prevent adaptations to, chronic ethanol treatment. Br J Pharmacol 103(3), 1669-1676 (1991).PubMedPubMedCentralCrossRefGoogle Scholar
  311. 311.
    Gatch MB. Nitrendipine blocks the nociceptive effects of chronically administered ethanol. Alcohol Clin Exp Res 26(8), 1181-1187 (2002).PubMedCrossRefGoogle Scholar
  312. 312.
    Rossetti ZL, Isola D, De Vry J, Fadda F. Effects of nimodipine on extracellular dopamine levels in the rat nucleus accumbens in ethanol withdrawal. Neuropharmacology 38(9), 1361-1369 (1999).PubMedCrossRefGoogle Scholar
  313. 313.
    Veatch LM, Gonzalez LP. Nifedipine alleviates alterations in hippocampal kindling after repeated ethanol withdrawal. Alcohol Clin Exp Res 24(4), 484-491 (2000).PubMedCrossRefGoogle Scholar
  314. 314.
    N'Gouemo P. Altered voltage-gated calcium channels in rat inferior colliculus neurons contribute to alcohol withdrawal seizures. Eur Neuropsychopharmacol 25(8), 1342-1352 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  315. 315.
    Hart C, Kisro NA, Robinson SL, Ksir C. Effects of the calcium channel blocker nimodipine on nicotine-induced locomotion in rats. Psychopharmacology (Berl) 128(4), 359-361 (1996).CrossRefGoogle Scholar
  316. 316.
    Biala G. Calcium channel antagonists suppress nicotine-induced place preference and locomotor sensitization in rodents. Pol J Pharmacol 55(3), 327-335 (2003).PubMedGoogle Scholar
  317. 317.
    Biala G, Weglinska B. Blockade of the expression of mecamylamine-precipitated nicotine withdrawal by calcium channel antagonists. Pharmacol Res 51(5), 483-488 (2005).PubMedCrossRefGoogle Scholar
  318. 318.
    Biala G, Budzynska B. Reinstatement of nicotine-conditioned place preference by drug priming: effects of calcium channel antagonists. Eur J Pharmacol 537(1-3), 85-93 (2006).PubMedCrossRefGoogle Scholar
  319. 319.
    Jackson KJ, Damaj MI. L-type calcium channels and calcium/calmodulin-dependent kinase II differentially mediate behaviors associated with nicotine withdrawal in mice. J Pharmacol Exp Ther 330(1), 152-161 (2009).PubMedPubMedCentralCrossRefGoogle Scholar
  320. 320.
    Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18(3), 247-291 (1993).PubMedCrossRefGoogle Scholar
  321. 321.
    Pierce RC, Kalivas PW. A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev 25(2), 192-216 (1997).PubMedCrossRefGoogle Scholar
  322. 322.
    Vanderschuren LJ, Pierce RC. Sensitization processes in drug addiction. Curr Top Behav Neurosci 3, 179-195 (2010).PubMedCrossRefGoogle Scholar
  323. 323.
    Stewart J. Review. Psychological and neural mechanisms of relapse. Philos Trans R Soc Lond B Biol Sci 363(1507), 3147-3158 (2008).PubMedPubMedCentralCrossRefGoogle Scholar
  324. 324.
    Nunes EJ, Hughley SM, Small KM, Rajadhyaksha AM, Addy NA. Ventral tegmental area L-type calcium channels mediate cue-induced cocaine seeking and dopamine release during early withdrawal. Program No. 351.05/FFF18, San Diego, CA(Society for Neuroscience), Online (2016).Google Scholar
  325. 325.
    Schierberl K, Hao J, Tropea TF, et al. Cav1.2 L-type Ca2+ channels mediate cocaine-induced GluA1 trafficking in the nucleus accumbens, a long-term adaptation dependent on ventral tegmental area Ca(v)1.3 channels. J Neurosci 31(38), 13562-13575 (2011).Google Scholar
  326. 326.
    Terrillion CE, Dao DT, Cachope R, et al. Reduced levels of Cacna1c attenuate mesolimbic dopamine system function. Genes Brain Behav 2017 Feb 10 [Epub ahead of print].Google Scholar
  327. 327.
    Liu Y, Harding M, Pittman A, et al. Cav1.2 and Cav1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area. J Neurophysiol 112(5), 1119-1130 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  328. 328.
    Wolf ME. Synaptic mechanisms underlying persistent cocaine craving. Nat Rev Neurosci 17(6), 351-365 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  329. 329.
    Enck RE. Understanding tolerance, physical dependence and addiction in the use of opioid analgesics. Am J Hosp Palliat Care 8(1), 9-11 (1991).PubMedCrossRefGoogle Scholar
  330. 330.
    Blasig J, Herz A, Reinhold K, Zieglgansberger S. Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33(1), 19-38 (1973).PubMedCrossRefGoogle Scholar
  331. 331.
    Wei E, Loh HH, Way EL. Quantitative aspects of precipitated abstinence in morphine-dependent rats. J Pharmacol Exp Ther 184(2), 398-403 (1973).PubMedGoogle Scholar
  332. 332.
    Shibasaki M, Kurokawa K, Mizuno K, Ohkuma S. Up-regulation of Ca(v)1.2 subunit via facilitating trafficking induced by Vps34 on morphine-induced place preference in mice. Eur J Pharmacol 651(1-3), 137-145 (2011).Google Scholar
  333. 333.
    Haller VL, Bernstein MA, Welch SP. Chronic morphine treatment decreases the Cav1.3 subunit of the L-type calcium channel. Eur J Pharmacol 578(2-3), 101-107 (2008).PubMedCrossRefGoogle Scholar
  334. 334.
    Roberto M, Gilpin NW, Siggins GR. The central amygdala and alcohol: role of gamma-aminobutyric acid, glutamate, and neuropeptides. Cold Spring Harb Perspect Med 2(12), a012195 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  335. 335.
    Silberman Y, Winder DG. Ethanol and corticotropin releasing factor receptor modulation of central amygdala neurocircuitry: an update and future directions. Alcohol 49(3), 179-184 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  336. 336.
    Zorumski CF, Mennerick S, Izumi Y. Acute and chronic effects of ethanol on learning-related synaptic plasticity. Alcohol 48(1), 1-17 (2014).PubMedCrossRefGoogle Scholar
  337. 337.
    N'Gouemo P, Morad M. Ethanol withdrawal seizure susceptibility is associated with upregulation of L- and P-type Ca2+ channel currents in rat inferior colliculus neurons. Neuropharmacology 45(3), 429-437 (2003).PubMedCrossRefGoogle Scholar
  338. 338.
    Littleton JM, Little HJ, Whittington MA. Effects of dihydropyridine calcium channel antagonists in ethanol withdrawal; doses required, stereospecificity and actions of Bay K 8644. Psychopharmacology (Berl) 100(3), 387-392 (1990).CrossRefGoogle Scholar
  339. 339.
    De Biasi M, Dani JA. Reward, addiction, withdrawal to nicotine. Annu Rev Neurosci 34, 105-130 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  340. 340.
    Katsura M, Mohri Y, Shuto K, et al. Up-regulation of L-type voltage-dependent calcium channels after long term exposure to nicotine in cerebral cortical neurons. J Biol Chem 277(10), 7979-7988 (2002).PubMedCrossRefGoogle Scholar
  341. 341.
    Hayashida S, Katsura M, Torigoe F, Tsujimura A, Ohkuma S. Increased expression of L-type high voltage-gated calcium channel alpha1 and alpha2/delta subunits in mouse brain after chronic nicotine administration. Brain Res Mol Brain Res 135(1-2), 280-284 (2005).PubMedCrossRefGoogle Scholar
  342. 342.
    Malin DH, Lake JR, Carter VA, et al. The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat. Psychopharmacology (Berl) 115(1-2), 180-184 (1994).CrossRefGoogle Scholar
  343. 343.
    Malin DH. Nicotine dependence: studies with a laboratory model. Pharmacol Biochem Behav 70(4), 551-559 (2001).PubMedCrossRefGoogle Scholar
  344. 344.
    Post RM, Kalivas P. Bipolar disorder and substance misuse: pathological and therapeutic implications of their comorbidity and cross-sensitisation. Br J Psychiatry 202(3), 172-176 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  345. 345.
    Lüthi A, Lüscher C. Pathological circuit function underlying addiction and anxiety disorders. Nat Neurosci 17(12), 1635-1643 (2014).PubMedCrossRefGoogle Scholar
  346. 346.
    Nestler EJ, Carlezon WA, Jr. The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59(12), 1151-1159 (2006).PubMedCrossRefGoogle Scholar
  347. 347.
    Russo SJ, Nestler EJ. The brain reward circuitry in mood disorders. Nat Rev Neurosci 14(9), 609-625 (2013).PubMedCrossRefGoogle Scholar
  348. 348.
    Sun H, Martin JA, Werner CT, et al. BAZ1B in nucleus accumbens regulates reward-related behaviors in response to distinct emotional stimuli. J Neurosci 36(14), 3954-3961 (2016).PubMedPubMedCentralCrossRefGoogle Scholar
  349. 349.
    Khibnik LA, Beaumont M, Doyle M, et al. Stress and cocaine trigger divergent and cell type-specific regulation of synaptic transmission at single spines in nucleus accumbens. Biol Psychiatry 79(11), 898-905 (2016).PubMedCrossRefGoogle Scholar
  350. 350.
    Lobo MK, Zaman S, Damez-Werno DM, et al. DeltaFosB induction in striatal medium spiny neuron subtypes in response to chronic pharmacological, emotional, and optogenetic stimuli. J Neurosci 33(47), 18381-18395 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  351. 351.
    Covington HE, 3rd, Maze I, Sun H, et al. A role for repressive histone methylation in cocaine-induced vulnerability to stress. Neuron 71(4), 656-670 (2011).PubMedPubMedCentralCrossRefGoogle Scholar
  352. 352.
    LaPlant Q, Vialou V, Covington HE, 3rd et al. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci 13(9), 1137-1143 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  353. 353.
    Chaudhury D, Walsh JJ, Friedman AK, et al. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493(7433), 532-536 (2013).PubMedCrossRefGoogle Scholar
  354. 354.
    Tye KM, Mirzabekov JJ, Warden MR, et al. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493(7433), 537-541 (2013).PubMedCrossRefGoogle Scholar
  355. 355.
    Walsh JJ, Han MH. The heterogeneity of ventral tegmental area neurons: Projection functions in a mood-related context. Neuroscience 282, 101-108 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  356. 356.
    Gunaydin LA, Grosenick L, Finkelstein JC, et al. Natural neural projection dynamics underlying social behavior. Cell 157(7), 1535-1551 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  357. 357.
    Covey DP, Roitman MF, Garris PA. Illicit dopamine transients: reconciling actions of abused drugs. Trends Neurosci 37(4), 200-210 (2014).PubMedPubMedCentralCrossRefGoogle Scholar
  358. 358.
    Nestler EJ. Role of the brain's reward circuitry in depression: transcriptional mechanisms. Int Rev Neurobiol 124, 151-170 (2015).PubMedPubMedCentralCrossRefGoogle Scholar
  359. 359.
    Russo SJ, Dietz DM, Dumitriu D, Morrison JH, Malenka RC, Nestler EJ. The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens. Trends Neurosci 33(6), 267-276 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  360. 360.
    Pascoli V, Terrier J, Hiver A, Luscher C. Sufficiency of mesolimbic dopamine neuron stimulation for the progression to addiction. Neuron, 88(5), 1054-1066 (2015).PubMedCrossRefGoogle Scholar
  361. 361.
    Saddoris MP, Sugam JA, Cacciapaglia F, Carelli RM. Rapid dopamine dynamics in the accumbens core and shell: learning and action. Front Biosci 5, 273-288 (2013).CrossRefGoogle Scholar
  362. 362.
    Goffer Y, Xu D, Eberle SE, et al. Calcium-permeable AMPA receptors in the nucleus accumbens regulate depression-like behaviors in the chronic neuropathic pain state. J Neurosci 33(48), 19034-19044 (2013).PubMedPubMedCentralCrossRefGoogle Scholar
  363. 363.
    Lim BK, Huang KW, Grueter BA, Rothwell PE, Malenka RC. Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens. Nature 487(7406), 183-189 (2012).PubMedPubMedCentralCrossRefGoogle Scholar
  364. 364.
    Vialou V, Robison AJ, Laplant QC, et al. DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nat Neurosci 13(6), 745-752 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  365. 365.
    Araki R, Ago Y, Hasebe S, et al. Involvement of prefrontal AMPA receptors in encounter stimulation-induced hyperactivity in isolation-reared mice. Int J Neuropsychopharmacol 17(6), 883-893 (2014).PubMedCrossRefGoogle Scholar
  366. 366.
    Wook Koo J, Labonte B, Engmann O, et al. Essential role of mesolimbic brain-derived neurotrophic factor in chronic social stress-induced depressive behaviors. Biol Psychiatry 80(6), 469-478 (2016).PubMedCrossRefGoogle Scholar
  367. 367.
    Lobo MK, Covington HE, 3rd, Chaudhury D, et al. Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science 330(6002), 385-390 (2010).PubMedPubMedCentralCrossRefGoogle Scholar
  368. 368.
    Le Moine C, Normand E, Bloch B. Phenotypical characterization of the rat striatal neurons expressing the D1 dopamine receptor gene. Proc Natl Acad Sci U S A 88(10), 4205-4209 (1991).PubMedPubMedCentralCrossRefGoogle Scholar
  369. 369.
    Lu XY, Ghasemzadeh MB, Kalivas PW. Expression of D1 receptor, D2 receptor, substance P and enkephalin messenger RNAs in the neurons projecting from the nucleus accumbens. Neuroscience 82(3), 767-780 (1998).PubMedCrossRefGoogle Scholar
  370. 370.
    Lohmann C. Calcium signaling and the development of specific neuronal connections. Prog Brain Res 175, 443-452 (2009).PubMedCrossRefGoogle Scholar
  371. 371.
    Ramocki MB, Zoghbi HY. Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature 455(7215), 912-918 (2008).PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2017

Authors and Affiliations

  • Zeeba D. Kabir
    • 1
    • 2
  • Arlene Martínez-Rivera
    • 1
    • 2
  • Anjali M. Rajadhyaksha
    • 1
    • 2
    • 3
  1. 1.Pediatric Neurology, PediatricsWeill Cornell MedicineNew YorkUSA
  2. 2.Weill Cornell Autism Research ProgramWeill Cornell MedicineNew YorkUSA
  3. 3.Feil Family Brain and Mind Research InstituteWeill Cornell MedicineNew YorkUSA

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