Advertisement

Neurobiology and Treatment of Anxiety: Signal Transduction and Neural Plasticity

  • C.H. Duman
  • R.S. Duman
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 169)

Abstract

The stress-dependence and chronic nature of anxiety disorders along with the anxiolytic effectiveness of antidepressant drugs suggests that neuronal plasticity may play a role in the pathophysiology of anxiety. Intracellular signaling pathways are known in many systems to be critical links in the cascades from surface signals to the molecular alterations that result in functional plasticity. Chronic antidepressant treatments can regulate intracellular signaling pathways and can induce molecular, cellular, and structural changes over time. These changes may be important to the anxiolytic effectiveness of these drugs. In addition, the signaling proteins implicated in the actions of chronic antidepressant action, such as cAMP response element binding protein (CREB), have also been implicated in conditioned fear and in anxiety. The cellular mechanisms underlying conditioned fear indicate roles for additional signaling pathways; however, less is known about such mechanisms in anxiety. The challenge to identify intracellular signaling pathways and related molecular and structural changes that are critical to the etiology and treatment of anxiety will further establish the importance of mechanisms of neuronal plasticity in functional outcome and improve treatment strategies.

Keywords

Antidepressant Calcium signaling cAMP cGMP-NOS signaling CREB Fear conditioning 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abel T, Nguyen PV, Marad M, Deuel TAS, Kandel ER, Bourtchouladze R (1997) Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell 88:615–626CrossRefPubMedGoogle Scholar
  2. Allen J, Allen CF (1974) Role of the amygdaloid complexes in the stress-induced release of ACTH in the rat. Neuroendocrinology 15:220–230PubMedGoogle Scholar
  3. Atkins C, Selcher JC, Petraitis JJ, Trzaskos JM, Sweatt JD (1998) The MAPK cascade is required for mammalian associative learning. Nat Neurosci 1:602–609CrossRefPubMedGoogle Scholar
  4. Barad M, Bourtchouladze R, Winder DG, Golan H, Kandel E (1998) Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proc Natl Acad Sci U S A 95:15020–15025PubMedGoogle Scholar
  5. Barros D, Izquierdo LA, Sant'Anna MK, Quevedo J, Medina JH, McGaugh JL, Izquierdo I (1999) Stimulators of the cAMP cascade reverse amnesia induced by intra-amygdala but intrahippocampal KN-62 administration. Neurobiol Learn Mem 71:94–103CrossRefPubMedGoogle Scholar
  6. Bauer E, LeDoux JE, Nader K (2001) Fear conditioning and LTP in the lateral amygdala are sensitive to the same stimulus contingencies. Nat Neurosci 4:687–688CrossRefPubMedGoogle Scholar
  7. Bauer E, Schafe GE, LeDoux J (2002) 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 22:5239–5249PubMedGoogle Scholar
  8. Berman D, Hazvi S, Rosenblum K, Seger R, Dudai Y(1998) Specific and differential activation of mitogen-activated protein kinase cascades by unfamiliar taste in the insular cortex of the behaving rat. J Neurosci 18:10037–10044PubMedGoogle Scholar
  9. Bernabeu R, Bevilaqua L, Ardenghi P, Bromberg E, Schmitz P, Bianchin M, Izquierdo I, Medina JH (1997) Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. Proc Natl Acad Sci U S A 94:7041–7046CrossRefPubMedGoogle Scholar
  10. Blair H, Schafe GE, Bauer EP, Rodrigues SM, LeDoux JE (2001) Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. Learn Mem 8:229–242CrossRefPubMedGoogle Scholar
  11. Blank T, Nijholt I, Grammatopoulos DK, Randeva HS, Hillhuse EW, Spiess J (2003) Corticotropin-releasing factor receptors couple to multiple G-proteins to activate diverse intracellular signaling pathways in mouse hippocampus: role in neuronal excitability and associative learning. J Neurosci 23:700–707PubMedGoogle Scholar
  12. Bliss T, Collingridge G (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39CrossRefPubMedGoogle Scholar
  13. Blum S, Adams AN, Dash PK (1999) A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory. J Neurosci 19:3535–3544PubMedGoogle Scholar
  14. Bogdan C (2001) Nitric oxide and the regulation of gene expression. Trends Cell Biol 11:66–75CrossRefPubMedGoogle Scholar
  15. Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79:59–68CrossRefPubMedGoogle Scholar
  16. Bourtchuladze R, Abel T, Berman N, Gordon R, Lapidus K, Kandel ER (1998) Different training procedures recruit either one or two critical periods for contextual memory consolidation, each of which requires protein synthesis and PKA. LearnMem 5:365–374Google Scholar
  17. Brambilla R, Gnesutta N, Minichiello L, White G, Roylance AJ, Herron CE, Ramsey M, Wolfer DP, Cestari V, Rossi-Arnaud C, Grant SG, Chapman PF, Lipp HP, Sturani E, Klein R (1997) A role for the Ras signalling pathway in synaptic transmission and long-term memory. Nature 390:281–286CrossRefPubMedGoogle Scholar
  18. Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick SM, Delaney RC, Mc-Carthy G, Charney DS, Innis RB (1995) MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry 152:973–981PubMedGoogle Scholar
  19. Brown T, Chapman PF, Kairiss EW, Keenan CL (1988) Long-term synaptic potentiation. Science 242:724–728PubMedGoogle Scholar
  20. Cahill L, McGaugh JL (1998) Mechanisms of emotional arousal and lasting declarative memory. Trends Neurosci 21:294–299CrossRefPubMedGoogle Scholar
  21. Campeau S, Miserendino MJD, Davis M (1992) Intra-amygdala infusion of the N-methyl-D-asparate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus. Behav Neurosci 106:569–574CrossRefPubMedGoogle Scholar
  22. Caton P, Tousman SA, Quock RM (1994) Involvement of nitric oxide in nitrous oxide anxiolysis in the elevated plus-maze. Pharmacol Biochem Behav 48:689–692CrossRefPubMedGoogle Scholar
  23. Chapman P, Kairiss EW, Keenan CL, Brown TH (1990) Long-term synaptic potentiation in the amygdala. Synapse 6:271–278CrossRefPubMedGoogle Scholar
  24. Chen A-H, Shirayama Y, Shin K-H, Neve RL, Duman RS (2001a) Expression of the cAMP response element binding protein (CREB) in hippocampus produces antidepressant effect. Biol Psychiatry 49:753–762CrossRefPubMedGoogle Scholar
  25. Chen F, Bilezikjian LM, Perrin MH, Rivier J, Vale W (1986) Corticotropin releasing factor receptor-mediated stimulation of adenylate cyclase activity in the rat brain. Brain Res 381:49–57CrossRefPubMedGoogle Scholar
  26. Conti A, Cryan JF, Dalvi A, Lucki L, Blendy JA (2002) CREB is essential for the upregulation of BDNF transcription, but not the behavioral or endocrine responses to antidepressant drugs. J Neurosci 22:3262–3268PubMedGoogle Scholar
  27. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartololomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A 98:12796–12801CrossRefPubMedGoogle Scholar
  28. Davis H, Squire LR (1984) Protein synthesis and memory: a review. Psychol Bull 96:518–559CrossRefPubMedGoogle Scholar
  29. Deisseroth K, Heist EK, Tsien RW (1998) Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature 392:198–202CrossRefPubMedGoogle Scholar
  30. Dinerman J, Dawson TM, Schell MJ, Snowman A, Synder SH (1994) Endothelial nitric oxide synthase localized to hippocampal pyramidal cells: implications for synaptic plasticity. Proc Natl Acad Sci U S A 91:4214–4218PubMedGoogle Scholar
  31. Dolmetsch R, Pajvani U, Fife K, Spotts JM, Greenberg ME (2001) Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway. Science 294:333–339CrossRefPubMedGoogle Scholar
  32. Duman R, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606PubMedGoogle Scholar
  33. Duman RS, Nestler EJ (1999) Cyclic nucleotides. In: Siegel GJ, Agranoff BW, Alberts RW (eds) Basic neurochemistry, 6th edn. Lippincott-Raven, Philadelphia, pp 433–452Google Scholar
  34. Duman R, Malberg J, Nakagawa S, D'Sa C (2000) Neuronal plasticity and survival in mood disorders. Biol Psychiatry 48:732–739CrossRefPubMedGoogle Scholar
  35. Dunn R, Reed TA, Copeland PD, Frye CA (1998) The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic efficacy without tolerance in rats following subchronic administration. Neuropharmacology 37:899–904CrossRefPubMedGoogle Scholar
  36. English J, Sweatt JD (1996) Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation. J Biol Chem 271:24329–24332CrossRefPubMedGoogle Scholar
  37. English J, Sweatt JD (1997) A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation. J Biol Chem 272:19103–19106CrossRefPubMedGoogle Scholar
  38. Falls W, Miserendino JD, Davis M (1992) Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala. J Neurosci 12:854–863PubMedGoogle Scholar
  39. Fanselow M, Kim JJ (1994) Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala. Behav Neurosci 108:210–212CrossRefPubMedGoogle Scholar
  40. Frey U, Huang YY, Kandel ER (1993) Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science 260:1661–1664PubMedGoogle Scholar
  41. Frisch C, Dere E, De Souza Silva MA, Godecke A, Schrader J, Huston JP (2000) Superior water maze performance and increase in fear-related behavior in the endothelial nitric oxide synthase-deficient mouse together with monoamine changes in cerebellum and ventral striatum. J Neurosci 20:6694–6700PubMedGoogle Scholar
  42. Goosens K, Holt W, Maren S (2000) A role for amygdaloid PKA and PKC in the acquisition of long-term conditional fear memories in rats. Behav Brain Res 114:145–152CrossRefPubMedGoogle Scholar
  43. Gould E, McEwen BS, Tanapat P, Galea LAM, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 17:2492–2498PubMedGoogle Scholar
  44. Griebel G, Misslin R, Vogel E, Bourguignon J (1991) Behavioral effects of rolipram and structurally related compounds in mice: behavioral sedation of cAMP phosphodiesterase inhibitors. J Neurochem 58:321–323Google Scholar
  45. Hardingham G, Arnold FJ, Bading H (2001) Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat Neurosci 4:261–267CrossRefPubMedGoogle Scholar
  46. Herman JP, Schafer MKH, Young EA, Thompson RC, Douglass JO, Akil H, Watson SJ (1989) Hippocampal regulation of the hypothalamo-pituitary-adrenocortical axis: in situ hybridization analysis of CRF and vasopressin messenger RNA expression in the hypothalamic paraventricular nucleus following hippocampectomy. J Neurosci 9:3072–3082PubMedGoogle Scholar
  47. Huag T, Storm JF (2000) Protein kinase A mediates the modulation of the slow Ca2+-dependent K+ current, IsAHP, by the neuropeptides CRF, VIP, and CGRP in hippocampal pyramidal neurons. J Neurophysiol 83:2071–2079PubMedGoogle Scholar
  48. Huang Y, Li X-C, Kandel ER (1994) cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase. Cell 79:69–79CrossRefPubMedGoogle Scholar
  49. Huang Y, Bach ME, Lipp HP, Zhuo M, Wolfer DP, Hawkins RD, Schoonjans L, Kandel ER, Godfraind JM, Mulligan R, Collen D, Carmeliet P (1996) Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation if both Schaffer collateral and mossy fiber pathways. Proc Natl Acad Sci U S A 93:8699–8704CrossRefPubMedGoogle Scholar
  50. Huang Y, Martin KC, Kandel ER (2000) Both protein kinase A and mitogen-activated protein kinase are required in the amygdala for the macromolecular synthesis-dependent late phase of long-term potentiation. J Neurosci 20:6317–6325PubMedGoogle Scholar
  51. Huang Y-Y, Kandel ER (1998) Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron 21:169–178CrossRefPubMedGoogle Scholar
  52. Impey S, Mark M, Villacres EC, Poser S, Chavkin C, Storm DR (1996) Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in CA1 of the hippocampus. Neuron 16:973–982CrossRefPubMedGoogle Scholar
  53. Impey S, Smith DM, Obrietan K, Donahue R, Wade C, Storm DR (1998) Stimulation of cAMP response element (CRE)-mediated transcription during contextual learning. Nat Neurosci 1:595–601CrossRefPubMedGoogle Scholar
  54. Josselyn S, Shi C, Carlezon WA, Neve RL, Nestler EJ, Davis M (2001) Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala. J Neurosci 21:2404–2412PubMedGoogle Scholar
  55. Kandel E (1997) Genes, synapses, and long-term memory. J Cell Physiol 173:124–125CrossRefPubMedGoogle Scholar
  56. Kang H, Sun LD, Atkins CM, Soderling TR, Wilson MA, Tonegawa S (2001) An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory. Cell 106:771–783CrossRefPubMedGoogle Scholar
  57. Kida S, Josselyn SA, Pena de Ortiz S, Kogan JH, Chevere I, Masushige S, Silva AJ (2002) CREB required for the stability of new and reactivated fear memories. Nat Neurosci 5:348–355CrossRefPubMedGoogle Scholar
  58. Kogan J, Frankland PW, Blendy JA, Coblentz J, Marowitz Z, Schutz G, Silva AJ (1996) Spaced training induces normal long-term memory in CREB mutant mice. Curr Biol 7:1–11CrossRefGoogle Scholar
  59. Koob G, Heinrichs SC (1999) A role for corticotropin releasing factor and urocortin in behavioral responses to stressors. Brain Res 848:141–152CrossRefPubMedGoogle Scholar
  60. LeDoux J (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184CrossRefPubMedGoogle Scholar
  61. Li S, Quock RM (2001) Comparison of N2O-and chlordiazepoxide-induced behaviors in the light/dark exploration test. Pharmacol Biochem Behav 68:789–796CrossRefPubMedGoogle Scholar
  62. Li S, Quock RM (2002) Effects of a nitric oxide donor on behavior and interaction with nitrous oxide in the mouse light/dark exploration test. Eur J Pharmacol 447:75–78CrossRefPubMedGoogle Scholar
  63. Li S, Yang D, Quock RM (2003a) Antisense knockdown of neuronal nitric oxide synthase antagonizes nitrous oxide-induced behavior. Brain Res 968:167–170CrossRefPubMedGoogle Scholar
  64. Li S, Yusuke O, Yang D, Quock RM (2003b) Antagonism of nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration procedure by pharmacologic disruption of endogenous nitric oxide function. Psychopharmacology (Berl) 166:366–372PubMedGoogle Scholar
  65. Li XB, Inoue T, Koyama T (2002) Effect of chronic treatment with the protein kinase C inhibitor staurosporine on the acquisition and expression of contextual fear conditioning. Eur J Pharmacol 441:151–155CrossRefPubMedGoogle Scholar
  66. Lin C-H, Yeh S-H, Lin C-H, Lu K-T, Leu T-H, Chang WOC, Gean P-W (2001) A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala. Neuron 31:841–851CrossRefPubMedGoogle Scholar
  67. Lin C-H, Yeh S-H, Leu T-H, Chang W-C, Wang S-T, Gean P-W (2003) Identification of calcineurin as a key signal in the extinction of fear memory. J Neurosci 23:1574–1579PubMedGoogle Scholar
  68. Lino de Oliveira C, Del Bel EA, Guimaraes FS (1997) Effects of L-NOARG on plus-maze performance in rats. Pharmacol Biochem Behav 56:55–59CrossRefPubMedGoogle Scholar
  69. Lu K, Walker DL, Davis M (2001) Mitogen-activated protein kinase cascade in the basolateral nucleusof amygdala is involved in extinction of fear-potentiatedstartle. J Neurosci 21:1–5Google Scholar
  70. Madini R, Hulo S, Toni N, Madani H, Steimer T, Muller D, Vassalli J (1999) Enhanced hippocampal long-term potentiation and learning by increased neuronal expression of tissue-type plasminogen activator in transgenic mice. EMBO J 18:3007–3012CrossRefPubMedGoogle Scholar
  71. Magarinos A, Deslandes A, McEwen BS (1999) Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress. Eur J Pharmacol 371:113–122CrossRefPubMedGoogle Scholar
  72. Malinow R, Schulman H, Tsien RW (1989) Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. Science 245:862–866PubMedGoogle Scholar
  73. Manji H, Drevets WC, Charney DS (2001b) The cellular neurobiology of depression. Nat Med 7:541–547CrossRefPubMedGoogle Scholar
  74. Mansuy I, Mayford M, jacob B, Kandel ER, Bach ME (1998) Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell 92:39–49CrossRefPubMedGoogle Scholar
  75. Margarinos A, McEwen BS, Flugge G, Fuchs E (1996) Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci 16:3534–3540PubMedGoogle Scholar
  76. Martin S, Grimwood PD, Morris RGM (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711CrossRefPubMedGoogle Scholar
  77. Mayford M, Bach ME, Huang YY, Wang L, Hawkins RD, Kandel ER (1996) Control of memory formation through regulated expression of a CaMKII transgene. Science 274:1678–1683CrossRefPubMedGoogle Scholar
  78. McEwen B (1999) Stress and hippocampal plasticity. Curr Opin Neurobiol 5:205–216CrossRefGoogle Scholar
  79. McGaugh JL, Ferry B, Vazdarjanova A, Roosedaal B (2000) Amygdala: role in modulation of memory storage. In: Aggleton JP (ed) The amygdala, 2nd edn. Oxford University Press, New York, pp 391–423Google Scholar
  80. McKernan M, Shinnick-Gallagher P (1997) Fear conditioning induces a lasting potentiation of synaptic currents in vitro. Nature 390:607–611CrossRefPubMedGoogle Scholar
  81. Mermelstein P, Bito H, Deisseroth K, Tsien RW (2000) Critical dependence of cAMP response element-binding protein phosphorylation on L-type calcium channels supports a selective response to EPSPs in preference to action potentials. J Neurosci 20:266–273PubMedGoogle Scholar
  82. Miller T, Tansey MG, Johnson EM, Greedon DJ (1997) Inhibition of phosphatidylinositol 3-kinase activity blocks depolarization and insulin-like growth factor 1-mediated survival of cerebellar granule cells. J Biol Chem 272:9847–9853PubMedGoogle Scholar
  83. Miserendino M, Sananes CB, Melia KR, Davis M (1990) Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala. Nature 345:716–718CrossRefPubMedGoogle Scholar
  84. Nakagawa S, Kim J-E, Lee R, Malberg JE, Chen J, Steffen C, Zhang Y-J, Nestler EJ, Duman RS (2002) Regulation of neurogenesis in adult mouse hippocampus by cAMP and cAMP response element-binding protein. J Neurosci 22:9868–9876PubMedGoogle Scholar
  85. Nelson R, Kriegseld LJ, Dawson VL, Dawson TM (1997b) Effects of nitric oxide on neuroendocrine function and behavior. Neuroendocrinology 18:463–491Google Scholar
  86. Nemeroff C, Widerlov E, Bissette G, Walleus H, Karlsson I, Eklund K, Kilts CD, Loosen PT, Vale W (1984) Elevated concentrations of CSF corticotropin releasing factor-like immunoreactivity in depressed patients. Science 226:1342–1344PubMedGoogle Scholar
  87. Nestler E, Terwilliger RZ, Duman RS (1989) Chronic antidepressant administration alters the subcellular distribution of cAMP-dependent protein kinase in rat frontal cortex. J Neurochem 53:1644–1647PubMedGoogle Scholar
  88. Nestler E, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM (2002a) Neurobiology of depression. Neuron 34:13–25CrossRefPubMedGoogle Scholar
  89. Nestler EJ, Duman RS (1999) G proteins. In: Siegel GJ, Agranoff BW, Alberts RW (eds) Basic neurochemistry, 6th edn. Lippincott-Raven, Philadelphia, pp 401–414Google Scholar
  90. Newton S, Thome J, Wallace TL, Shirayama Y, Schlesinger L, Sakai N, Chen N, Neve R, Nestler EJ, Duman RS (2002b) Inhibition of cAMP response element-binding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect. J Neurosci 24:10883–10890Google Scholar
  91. Nguyen P, Kandel ER (1996) A macromolecular synthesis-dependent late phase of long-term potentiation requiring cAMP in the medial perforant pathway of rat hippocampal slices. J Neurosci 16:3189–3198PubMedGoogle Scholar
  92. Nibuya M, Nestler EJ, Duman RS (1996) Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 16:2365–2372PubMedGoogle Scholar
  93. Pawlak R, Magarinos AM, Melchor J, McEwen B, Strickland S (2003) Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior. Nat Neurosci 6:168–174CrossRefPubMedGoogle Scholar
  94. Perez J, Tinelli D, Brunello N, Racagni G (1989) cAMP-dependent phosphorylation of soluble and crude microtubule fractions of rat cerebral cortex after prolonged desmethylimipramine treatment. Eur J Pharmacol 172:305–316CrossRefPubMedGoogle Scholar
  95. Pliakas A, Carlson RR, Neve RL, Konradi C, Nestler EJ, Carlezon WA (2001) Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated CREB expression in the nucleus accumbens. J Neurosci 21:7397–7403PubMedGoogle Scholar
  96. Popoli M, Vocaturo C, Perez J, Smeraldi E, Racagni G (1995) Presynaptic Ca2+/calmodulindependent protein kinase II: autophosphorylation and activity increase in the hippocampus after long-term blockade of serotonin reuptake. Mol Pharmacol 48:623–629PubMedGoogle Scholar
  97. Popoli M, Venegoni A, Vocaturo C, Buffa L, Perez J, Smeraldi E, Racagni G (1997a) Long-term blockade of serotonin reuptake affects synaptotagmin phosphorylation in the hippocampus. Mol Pharmacol 51:19–26PubMedGoogle Scholar
  98. Popoli M, Zanotti S, Radaelli R, Gaggianesi C, Verona M, Brunello N, Racagni G (1997b) The neurotransmitter release machinery as a site of action for psychotropic drugs: effect of typical and atypical antidepressants. Soc Neurosci Abstr 2325Google Scholar
  99. Prast H, Philippu A (2001) Nitric oxide as modulator of neuronal function. Prog Neurobiol 64:51–68CrossRefPubMedGoogle Scholar
  100. Quock R, Nguyen E (1992) Possible involvement of nitric oxide in chlordiazepoxide-induced anxiolysis in rats. Life Sci 51:255–260CrossRefGoogle Scholar
  101. Reyman K, Brodemann R, Kase H, Matthies H (1988) Inhibitors of calmodulin and protein kinase C block different phases of hippocampal long-term potentiation. Brain Res 461:388–392CrossRefPubMedGoogle Scholar
  102. Roberson E, Sweatt JD (1996) Transient activation of cyclic AMP-dependent protein kinase during hippocampal long-term potentiation. J Biol Chem 271:30436–30441CrossRefPubMedGoogle Scholar
  103. Rodrigues S, Schafe GE, LeDoux JE (2001) Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning. J Neurosci 21:6889–6896PubMedGoogle Scholar
  104. Rogan M, LeDoux JE (1995) LTPis accompanied by commensurate enhancement of auditory-evoked responses in a fear conditioning circuit. Neuron 15:127–136CrossRefPubMedGoogle Scholar
  105. Rogan M, Staubli U, LeDoux J (1997) Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390:604–607CrossRefPubMedGoogle Scholar
  106. Russell DS, Duman RS (2002) Neurotrophic factors and intracellular signal transduction pathways. In: Davis KL, Charney D, Coyle JT, Nemeroff C (eds) Neuropsychopharmacology: the fifth generation of progress. Lippincott Williams and Wilkins, Philadelphia, pp 207–215Google Scholar
  107. Schaefer M, Wong ST, Wozniak DF, Muglia LM, Liauw JA, Zhuo M, Nardi A, Hartman RE, Vogt SK, Luedke CE, Storm DR, Muglia LJ (2000) Alteredstress-induce anxiety in adenylyl cyclase type VIII-deficient mice. J Neurosci 20:4809–4820PubMedGoogle Scholar
  108. Schafe G, LeDoux JE (2000) Memory consolidation of auditory Pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala. J Neurosci 20:1–5PubMedGoogle Scholar
  109. Schafe G, Nadel NV, Sullivan GM, Harris A, LeDoux JE (1999) Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA and MAP Kinase. Learn Mem 6:97–110PubMedGoogle Scholar
  110. Schafe G, Atkins CM, Swank MW, Bauer EP, Sweatt JD, LeDoux JE (2000) Activation of ERK/MAP Kinase in the amygdala is required for memory consolidation of Pavlovian fear conditioning. J Neurosci 20:8177–8187PubMedGoogle Scholar
  111. Schafe G, Nader K, Blair HT, LeDoux JE (2001) Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective. Trends Neurosci 24:540–546CrossRefPubMedGoogle Scholar
  112. Schuman E, Madison DV (1991) A requirement for the intercellular messenger nitric oxide in long-term potentiation. Science 254:1503–1506PubMedGoogle Scholar
  113. Selcher J, Atkins CM, Trzaskos JM, Paylor R, Sweatt JD (1999) A necessity for MAP kinase activation in mammalian spatial learning. Learn Mem 6:478–490CrossRefPubMedGoogle Scholar
  114. Sheline Y, Wany P, Gado MH, Csernansky JG, Vannier MW(1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A 93:3908–3913CrossRefPubMedGoogle Scholar
  115. Shirayama Y, Nakagawa S, Chen AC-H, Russel DS, and Duman RS (2002) Brain derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22:3251–3261PubMedGoogle Scholar
  116. Silva A, Rosahl TW, Chapman PF, Marowitz Z, Friedman E, Frankland PW, Cestari V, Cioffi D, Sadhof TC, Bourtchuladze R (1996) Impaired learning in mice with abnormal short-lived plasticity. Curr Biol 6:1509–1518CrossRefPubMedGoogle Scholar
  117. Silva A, Kogan JH, Frankland PW, Kida S (1998) CREB and memory. Annu Rev Neurosci 21:127–148CrossRefPubMedGoogle Scholar
  118. Silvestre J, Fernandez AG, Palacios JN (1999) Effects of rolipram on the elevated plus-maze test in rats: a preliminary study. J Psychopharmacol 13:274–277PubMedGoogle Scholar
  119. Sousa N, Lukoyanov NV, Madeira MD, Almeida OF, Paula-Barbosa MM (2000) Reorganization of the morphology of hippocampal neurites and synapsed after stress-induced damage correlates with behavioral improvements. Neuroscience 97:253–266CrossRefPubMedGoogle Scholar
  120. Stanciu M, Radulovic J, Spiess J (2001) Phosphorylated cAMP response element binding protein in the mouse brain after fear conditioning: relationship to Fos production. Mol Brain Res 94:15–24CrossRefPubMedGoogle Scholar
  121. Sweatt J (2001) The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76:1–10CrossRefPubMedGoogle Scholar
  122. Szapiro G, Vianna MRM, McGaugh JL, Medina JH, Izquierdo I (2003) The role of NMDA glutamate receptors, PKA, MAPK, and CAMKII in the hippocampus in extinction of conditioned fear. Hippocampus 13:53–58CrossRefPubMedGoogle Scholar
  123. Thome J, Sakai N, Shin KH, Steffen C, Zhang Y-J, Impey S, Storm DR, Duman RS (2000) cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 20:4030–4036PubMedGoogle Scholar
  124. Vale A, Green S, Montgomery AM, Shafi S (1998) The nitric oxide synthesis inhibitor LNAME produces anxiogenic-like effects in the rat elevated plus-maze test, but not in the social interaction test. J Psychopharmacol 12:268–272PubMedGoogle Scholar
  125. Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and β-endorphin. Science 213:1394–1397PubMedGoogle Scholar
  126. Verona M, Zanotti S, Gggianesi C, Schafer T, Racagni G, Popoli M (1998) Modulation of protein-protein interaction in presynaptic terminals: a possible sit of action for psychotropic drugs. Int J Neuorpsychopharm Suppl 1Google Scholar
  127. Vianna M, Szapiro G, McGaugh JL, Medina JH, Izquierdo I (2001) Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus. Proc Natl Acad Sci U S A 98:12251–12254CrossRefPubMedGoogle Scholar
  128. Volke V, Soosaar A, Koks S, Bourin M, Mannisto PT, Vasar E (1997) 7-Nitroindazole, a nitric oxide synthase inhibitor, has anxiolytic-like properties in exploratory models of anxiety. Psychopharmacology (Berl) 131:399–405CrossRefPubMedGoogle Scholar
  129. Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S (2002) Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci 22:6810–6818PubMedGoogle Scholar
  130. Watanabe Y, Gould E, McEwen BS (1992a) Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341–345CrossRefPubMedGoogle Scholar
  131. Weeber E, Atkins CM, Selcher JC, Varga AW, Mirnikjoo B, Paylor R, Leitges M, Sweatt JD (2000) A role for the β isoform of protein kinase C in fear conditioning. J Neurosci 20:5906–5914PubMedGoogle Scholar
  132. Weisskopf M, Bauer EP, LeDoux JE (1999) L-Type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala. J Neurosci 19:10512–10519PubMedGoogle Scholar
  133. Wolfman C, Fin C, Dias M, Bianchin M, Da Silva RC, Schmitz PK, Medina JH, Izquierdo I (1994) Intrahippocampal or intraamygdala infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II, causes retrograde amnesia in the rat. Behav Neural Biol 61:203–205PubMedGoogle Scholar
  134. Yao R, Cooper GM (1995) Requirement for phosphatidyl-inositol 3-kinase in the prevention of apoptosis by nerve growth factor. Science 267:2003–2006PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • C.H. Duman
    • 1
  • R.S. Duman
    • 1
  1. 1.Laboratory of Molecular Psychiatry, Departments of Psychiatry and PharmacologyYale University School of MedicineNew HavenUSA

Personalised recommendations