The Cerebellar GABAAR System as a Potential Target for Treating Alcohol Use Disorder

  • David J. RossiEmail author
  • Ben D. Richardson
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 248)


In the brain, fast inhibitory neurotransmission is mediated primarily by the ionotropic subtype of the gamma-aminobutyric acid (GABA) receptor subtype A (GABAAR). It is well established that the brain’s GABAAR system mediates many aspects of neurobehavioral responses to alcohol (ethanol; EtOH). Accordingly, in both preclinical studies and some clinical scenarios, pharmacologically targeting the GABAAR system can alter neurobehavioral responses to acute and chronic EtOH consumption. However, many of the well-established interactions of EtOH and the GABAAR system have been identified at concentrations of EtOH ([EtOH]) that would only occur during abusive consumption of EtOH (≥40 mM), and there are still inadequate treatment options for prevention of or recovery from alcohol use disorder (AUD, including abuse and dependence). Accordingly, there is a general acknowledgement that more research is needed to identify and characterize: (1) neurobehavioral targets of lower [EtOH] and (2) associated brain structures that would involve such targets in a manner that may influence the development and maintenance of AUDs.

Nearly 15 years ago it was discovered that the GABAAR system of the cerebellum is highly sensitive to EtOH, responding to concentrations as low as 10 mM (as would occur in the blood of a typical adult human after consuming 1–2 standard units of EtOH). This high sensitivity to EtOH, which likely mediates the well-known motor impairing effects of EtOH, combined with recent advances in our understanding of the role of the cerebellum in non-motor, cognitive/emotive/reward processes has renewed interest in this system in the specific context of AUD. In this chapter we will describe recent advances in our understanding of cerebellar processing, actions of EtOH on the cerebellar GABAAR system, and the potential relationship of such actions to the development of AUD. We will finish with speculation about how cerebellar specific GABAAR ligands might be effective pharmacological agents for treating aspects of AUD.


Addiction Alcohol AUD Cerebellum Ethanol GABA 



This work was supported by National Institute on Alcohol Abuse and Alcoholism Grants R01AA-012439 and R01AA-026078, and Washington State University Alcohol and Drug Abuse Research Program (ADARP) grant to D.J.R., and by an ADARP postdoctoral grant to B.D.R.


  1. Allan AM, Harris RA (1986) Gamma-aminobutyric acid and alcohol actions: neurochemical studies of long sleep and short sleep mice. Life Sci 39:2005–2015PubMedGoogle Scholar
  2. Allan AM, Harris RA (1987) Involvement of neuronal chloride channels in ethanol intoxication, tolerance, and dependence. Recent Dev Alcohol 5:313–325PubMedGoogle Scholar
  3. Allan AM, Huidobro-Toro JP, Bleck V, Harris RA (1987) Alcohol and the GABA receptor-chloride channel complex of brain. Alcohol Alcohol Suppl 1:643–646PubMedGoogle Scholar
  4. Allan AM, Spuhler KP, Harris RA (1988) Gamma-aminobutyric acid-activated chloride channels: relationship to genetic differences in ethanol sensitivity. J Pharmacol Exp Ther 244:866–870PubMedGoogle Scholar
  5. Anton RF, Schacht JP, Book SW (2014) Pharmacologic treatment of alcoholism. Handb Clin Neurol 125:527–542PubMedGoogle Scholar
  6. Avegno EM, Salling MC, Borgkvist A, Mrejeru A, Whitebirch AC, Margolis EB, Sulzer D, Harrison NL (2016) Voluntary adolescent drinking enhances excitation by low levels of alcohol in a subset of dopaminergic neurons in the ventral tegmental area. Neuropharmacology 110:386–395PubMedPubMedCentralGoogle Scholar
  7. Bagnall MW, Zingg B, Sakatos A, Moghadam SH, Zeilhofer HU, du LS (2009) Glycinergic projection neurons of the cerebellum. J Neurosci 29:10104–10110PubMedPubMedCentralGoogle Scholar
  8. Banks MI, Pearce RA (2000) Kinetic differences between synaptic and extrasynaptic GABA(A) receptors in CA1 pyramidal cells. J Neurosci 20:937–948PubMedGoogle Scholar
  9. Barmack NH, Yakhnitsa V (2008) Functions of interneurons in mouse cerebellum. J Neurosci 28:1140–1152PubMedGoogle Scholar
  10. Basile A, Hoffer B, Dunwiddie T (1983) Differential sensitivity of cerebellar purkinje neurons to ethanol in selectively outbred lines of mice: maintenance in vitro independent of synaptic transmission. Brain Res 264:69–78PubMedGoogle Scholar
  11. Baumann O, Borra RJ, Bower JM, Cullen KE, Habas C, Ivry RB, Leggio M, Mattingley JB, Molinari M, Moulton EA, Paulin MG, Pavlova MA, Schmahmann JD, Sokolov AA (2015) Consensus paper: the role of the cerebellum in perceptual processes. Cerebellum 14:197–220PubMedGoogle Scholar
  12. Beckstead RM, Domesick VB, Nauta WJ (1979) Efferent connections of the substantia nigra and ventral tegmental area in the rat. Brain Res 175:191–217PubMedGoogle Scholar
  13. Bell RL, Stewart RB, Woods JE, Lumeng L, Li TK, Murphy JM, McBride WJ (2001) Responsivity and development of tolerance to the motor impairing effects of moderate doses of ethanol in alcohol-preferring (P) and -nonpreferring (NP) rat lines. Alcohol Clin Exp Res 25:644–650PubMedGoogle Scholar
  14. Bell RL, Rodd ZA, Lumeng L, Murphy JM, McBride WJ (2006) The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addict Biol 11:270–288PubMedGoogle Scholar
  15. Ben-Ari Y, Woodin MA, Sernagor E, Cancedda L, Vinay L, Rivera C, Legendre P, Luhmann HJ, Bordey A, Wenner P, Fukuda A, van den Pol AN, Gaiarsa JL, Cherubini E (2012) Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever! Front Cell Neurosci 6:35PubMedPubMedCentralGoogle Scholar
  16. Billard JM, Vigot R, Batini C (1993) GABA, THIP and baclofen inhibition of Purkinje cells and cerebellar nuclei neurons. Neurosci Res 16:65–69PubMedGoogle Scholar
  17. Bjork JM, Gilman JM (2014) The effects of acute alcohol administration on the human brain: insights from neuroimaging. Neuropharmacology 84:101–110PubMedGoogle Scholar
  18. Bledsoe J, Semrud-Clikeman M, Pliszka SR (2009) A magnetic resonance imaging study of the cerebellar vermis in chronically treated and treatment-naive children with attention-deficit/hyperactivity disorder combined type. Biol Psychiatry 65:620–624PubMedPubMedCentralGoogle Scholar
  19. Boehm SL, Ponomarev I, Jennings AW, Whiting PJ, Rosahl TW, Garrett EM, Blednov YA, Harris RA (2004) Gamma-aminobutyric acid A receptor subunit mutant mice: new perspectives on alcohol actions. Biochem Pharmacol 68:1581–1602PubMedGoogle Scholar
  20. Borghese CM, Harris RA (2007) Studies of ethanol actions on recombinant delta-containing gamma-aminobutyric acid type A receptors yield contradictory results. Alcohol 41:155–162PubMedPubMedCentralGoogle Scholar
  21. Borghese CM, Storustovu S, Ebert B, Herd MB, Belelli D, Lambert JJ, Marshall G, Wafford KA, Harris RA (2006) The delta subunit of gamma-aminobutyric acid type A receptors does not confer sensitivity to low concentrations of ethanol. J Pharmacol Exp Ther 316:1360–1368PubMedPubMedCentralGoogle Scholar
  22. Borghese CM, Ruiz CI, Lee US, Cullins MA, Bertaccini EJ, Trudell JR, Harris RA (2016) Identification of an inhibitory alcohol binding site in GABAA rho1 receptors. ACS Chem Neurosci 7:100–108PubMedPubMedCentralGoogle Scholar
  23. Botta P, Mameli M, Floyd KL, Radcliffe RA, Valenzuela CF (2007a) Ethanol sensitivity of GABAergic currents in cerebellar granule neurons is not increased by a single amino acid change (R100Q) in the alpha6 GABAA receptor subunit. J Pharmacol Exp Ther 323:684–691PubMedPubMedCentralGoogle Scholar
  24. Botta P, Radcliffe RA, Carta M, Mameli M, Daly E, Floyd KL, Deitrich RA, Valenzuela CF (2007b) Modulation of GABAA receptors in cerebellar granule neurons by ethanol: a review of genetic and electrophysiological studies. Alcohol 41:187–199PubMedPubMedCentralGoogle Scholar
  25. Botta P, de Souza FM, Sangrey T, De Schutter E, Valenzuela CF (2010) Alcohol excites cerebellar Golgi cells by inhibiting the Na+/K+ ATPase. Neuropsychopharmacology 35:1984–1996PubMedPubMedCentralGoogle Scholar
  26. Botta P, Simoes de Souza FM, Sangrey T, De Schutter E, Valenzuela CF (2012) Excitation of rat cerebellar Golgi cells by ethanol: further characterization of the mechanism. Alcohol Clin Exp Res 36:616–624PubMedPubMedCentralGoogle Scholar
  27. Boyle AE, Segal R, Smith BR, Amit Z (1993) Bidirectional effects of GABAergic agonists and antagonists on maintenance of voluntary ethanol intake in rats. Pharmacol Biochem Behav 46:179–182PubMedPubMedCentralGoogle Scholar
  28. Bragina L, Marchionni I, Omrani A, Cozzi A, Pellegrini-Giampietro DE, Cherubini E, Conti F (2008) GAT-1 regulates both tonic and phasic GABA(A) receptor-mediated inhibition in the cerebral cortex. J Neurochem 105:1781–1793PubMedPubMedCentralGoogle Scholar
  29. Brickley SG, Cull-Candy SG, Farrant M (1996) Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol 497(Pt 3):753–759PubMedPubMedCentralGoogle Scholar
  30. Brickley SG, Revilla V, Cull-Candy SG, Wisden W, Farrant M (2001) Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Nature 409:88–92PubMedPubMedCentralGoogle Scholar
  31. Brodie MS, Appel SB (2000) Dopaminergic neurons in the ventral tegmental area of C57BL/6J and DBA/2J mice differ in sensitivity to ethanol excitation. Alcohol Clin Exp Res 24:1120–1124PubMedPubMedCentralGoogle Scholar
  32. Brodie MS, Shefner SA, Dunwiddie TV (1990) Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 508:65–69PubMedGoogle Scholar
  33. Cagetti E, Liang J, Spigelman I, Olsen RW (2003) Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol 63:53–64PubMedGoogle Scholar
  34. Carta M, Mameli M, Valenzuela CF (2004) Alcohol enhances GABAergic transmission to cerebellar granule cells via an increase in Golgi cell excitability. J Neurosci 24:3746–3751PubMedPubMedCentralGoogle Scholar
  35. Cathala L, Misra C, Cull-Candy S (2000) Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses. J Neurosci 20:5899–5905PubMedPubMedCentralGoogle Scholar
  36. Cathala L, Brickley S, Cull-Candy S, Farrant M (2003) Maturation of EPSCs and intrinsic membrane properties enhances precision at a cerebellar synapse. J Neurosci 23:6074–6085PubMedPubMedCentralGoogle Scholar
  37. Cavdar S, Onat F, Aker R, Sehirli U, San T, Yananli HR (2001a) The afferent connections of the posterior hypothalamic nucleus in the rat using horseradish peroxidase. J Anat 198:463–472PubMedPubMedCentralGoogle Scholar
  38. Cavdar S, San T, Aker R, Sehirli U, Onat F (2001b) Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat. J Anat 198:37–45PubMedPubMedCentralGoogle Scholar
  39. Cavelier P, Hamann M, Rossi D, Mobbs P, Attwell D (2005) Tonic excitation and inhibition of neurons: ambient transmitter sources and computational consequences. Prog Biophys Mol Biol 87:3–16PubMedPubMedCentralGoogle Scholar
  40. Chen S, Hillman DE (1993) Colocalization of neurotransmitters in the deep cerebellar nuclei. J Neurocytol 22:81–91PubMedPubMedCentralGoogle Scholar
  41. Choi DS, Wei W, Deitchman JK, Kharazia VN, Lesscher HM, McMahon T, Wang D, Qi ZH, Sieghart W, Zhang C, Shokat KM, Mody I, Messing RO (2008) Protein kinase Cdelta regulates ethanol intoxication and enhancement of GABA-stimulated tonic current. J Neurosci 28:11890–11899PubMedPubMedCentralGoogle Scholar
  42. Church AC, Fuller JL, Dann L (1979) Alcohol intake in selected lines of mice: importance of sex and genotype. J Comp Physiol Psychol 93:242–246PubMedPubMedCentralGoogle Scholar
  43. Cook JB, Dumitru AM, O'Buckley TK, Morrow AL (2014) Ethanol administration produces divergent changes in GABAergic neuroactive steroid immunohistochemistry in the rat brain. Alcohol Clin Exp Res 38:90–99PubMedPubMedCentralGoogle Scholar
  44. Crabbe JC, Metten P, Ponomarev I, Prescott CA, Wahlsten D (2006a) Effects of genetic and procedural variation on measurement of alcohol sensitivity in mouse inbred strains. Behav Genet 36:536–552PubMedPubMedCentralGoogle Scholar
  45. Crabbe JC, Phillips TJ, Harris RA, Arends MA, Koob GF (2006b) Alcohol-related genes: contributions from studies with genetically engineered mice. Addict Biol 11:195–269PubMedPubMedCentralGoogle Scholar
  46. Crabbe JC, Bell RL, Ehlers CL (2010) Human and laboratory rodent low response to alcohol: is better consilience possible? Addict Biol 15:125–144PubMedPubMedCentralGoogle Scholar
  47. Crews FT, Morrow AL, Criswell H, Breese G (1996) Effects of ethanol on ion channels. Int Rev Neurobiol 39:283–367PubMedPubMedCentralGoogle Scholar
  48. Criswell HE, Ming Z, Kelm MK, Breese GR (2008) Brain regional differences in the effect of ethanol on GABA release from presynaptic terminals. J Pharmacol Exp Ther 326:596–603PubMedPubMedCentralGoogle Scholar
  49. Cservenka A, Nagel BJ (2012) Risky decision-making: an fMRI study of youth at high risk for alcoholism. Alcohol Clin Exp Res 36(4):604–615PubMedPubMedCentralGoogle Scholar
  50. Cservenka A, Casimo K, Fair DA, Nagel BJ (2014) Resting state functional connectivity of the nucleus accumbens in youth with a family history of alcoholism. Psychiatry Res 221:210–219PubMedGoogle Scholar
  51. Damji KF, Allingham RR, Pollock SC, Small K, Lewis KE, Stajich JM, Yamaoka LH, Vance JM, Pericak-Vance MA (1996) Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias. Arch Neurol 53:338–344PubMedGoogle Scholar
  52. Daoust M, Lhuintre JP, Moore N, Saligaut C, Flipo JL, Boismare F (1987) Is initial sensitivity to ethanol correlated with alcohol preference in alcohol-drinking and non-drinking rats? Alcohol Alcohol 22:409–414PubMedGoogle Scholar
  53. Dar MS (2015) Ethanol-induced cerebellar ataxia: cellular and molecular mechanisms. Cerebellum 14:447–465PubMedGoogle Scholar
  54. Daurio AM, Aston SA, Schwandt ML, Bukhari MO, Bouhlal S, Farokhnia M, Lee MR, Leggio L (2017) Impulsive personality traits mediate the relationship between adult attention deficit hyperactivity symptoms and alcohol dependence severity. Alcohol Clin Exp Res 42(1):173–183PubMedPubMedCentralGoogle Scholar
  55. Davies M (2003) The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. J Psychiatry Neurosci 28:263–274PubMedPubMedCentralGoogle Scholar
  56. Dayas CV, McGranahan TM, Martin-Fardon R, Weiss F (2008) Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse. Biol Psychiatry 63:152–157PubMedGoogle Scholar
  57. De Zeeuw CI, Berrebi AS (1995) Postsynaptic targets of Purkinje cell terminals in the cerebellar and vestibular nuclei of the rat. Eur J Neurosci 7:2322–2333PubMedGoogle Scholar
  58. Deik A, Saunders-Pullman R, Luciano MS (2012) Substance of abuse and movement disorders: complex interactions and comorbidities. Curr Drug Abuse Rev 5:243–253PubMedPubMedCentralGoogle Scholar
  59. Deitrich RA, Dunwiddie TV, Harris RA, Erwin VG (1989) Mechanism of action of ethanol: initial central nervous system actions. Pharmacol Rev 41:489–537PubMedPubMedCentralGoogle Scholar
  60. Dempsey CW, Richardson DE (1987) Paleocerebellar stimulation induces in vivo release of endogenously synthesized [3H]dopamine and [3H]norepinephrine from rat caudal dorsomedial nucleus accumbens. Neuroscience 21:565–571PubMedGoogle Scholar
  61. Diaz MR, Valenzuela CF (2016) Sensitivity of GABAergic tonic currents to acute ethanol in cerebellar granule neurons is not age- or delta subunit-dependent in developing rats. Alcohol Clin Exp Res 40:83–92PubMedPubMedCentralGoogle Scholar
  62. Diaz MR, Wadleigh A, Hughes BA, Woodward JJ, Valenzuela CF (2011) Bestrophin1 channels are insensitive to ethanol and do not mediate tonic GABAergic currents in cerebellar granule cells. Front Neurosci 5:148PubMedGoogle Scholar
  63. Ding ZM, Rodd ZA, Engleman EA, McBride WJ (2009) Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol. Alcohol Clin Exp Res 33:1571–1581PubMedPubMedCentralGoogle Scholar
  64. Ding ZM, Oster SM, Hall SR, Engleman EA, Hauser SR, McBride WJ, Rodd ZA (2011) The stimulating effects of ethanol on ventral tegmental area dopamine neurons projecting to the ventral pallidum and medial prefrontal cortex in female Wistar rats: regional difference and involvement of serotonin-3 receptors. Psychopharmacology 216:245–255PubMedPubMedCentralGoogle Scholar
  65. Eastes LE (2010) Alcohol withdrawal syndrome in trauma patients: a review. J Emerg Nurs 36:507–509PubMedGoogle Scholar
  66. Ebralidze AK, Rossi DJ, Tonegawa S, Slater NT (1996) Modification of NMDA receptor channels and synaptic transmission by targeted disruption of the NR2C gene. J Neurosci 16:5014–5025PubMedGoogle Scholar
  67. Eilers J, Plant TD, Marandi N, Konnerth A (2001) GABA-mediated Ca2+ signalling in developing rat cerebellar Purkinje neurones. J Physiol 536:429–437PubMedPubMedCentralGoogle Scholar
  68. Elmer GI, Meisch RA, Goldberg SR, George FR (1990) Ethanol self-administration in long sleep and short sleep mice indicates reinforcement is not inversely related to neurosensitivity. J Pharmacol Exp Ther 254:1054–1062PubMedGoogle Scholar
  69. Enoch MA, Hodgkinson CA, Shen PH, Gorodetsky E, Marietta CA, Roy A, Goldman D (2016) GABBR1 and SLC6A1, two genes involved in modulation of GABA synaptic transmission, influence risk for alcoholism: results from three ethnically diverse populations. Alcohol Clin Exp Res 40:93–101PubMedPubMedCentralGoogle Scholar
  70. Epstein JN, Casey BJ, Tonev ST, Davidson MC, Reiss AL, Garrett A, Hinshaw SP, Greenhill LL, Glover G, Shafritz KM, Vitolo A, Kotler LA, Jarrett MA, Spicer J (2007) ADHD- and medication-related brain activation effects in concordantly affected parent-child dyads with ADHD. J Child Psychol Psychiatry 48:899–913PubMedGoogle Scholar
  71. Erwin VG, McClearn GE, Kuse AR (1980) Interrelationships of alcohol consumption, actions of alcohol, and biochemical traits. Pharmacol Biochem Behav 13(Suppl 1):297–302PubMedGoogle Scholar
  72. Fallon JH, Koziell DA, Moore RY (1978) Catecholamine innervation of the basal forebrain. II. Amygdala, suprarhinal cortex and entorhinal cortex. J Comp Neurol 180:509–532PubMedGoogle Scholar
  73. Ferrucci R, Giannicola G, Rosa M, Fumagalli M, Boggio PS, Hallett M, Zago S, Priori A (2012) Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness. Cognit Emot 26:786–799Google Scholar
  74. Fidler TL, Bakner L, Cunningham CL (2004) Conditioned place aversion induced by intragastric administration of ethanol in rats. Pharmacol Biochem Behav 77:731–743PubMedGoogle Scholar
  75. Fidler TL, Dion AM, Powers MS, Ramirez JJ, Mulgrew JA, Smitasin PJ, Crane AT, Cunningham CL (2011) Intragastric self-infusion of ethanol in high- and low-drinking mouse genotypes after passive ethanol exposure. Genes Brain Behav 10:264–275PubMedGoogle Scholar
  76. Finn DA, Ford MM, Wiren KM, Roselli CE, Crabbe JC (2004) The role of pregnane neurosteroids in ethanol withdrawal: behavioral genetic approaches. Pharmacol Ther 101:91–112PubMedGoogle Scholar
  77. Freund RK, Wang Y, Palmer MR (1993) Differential effects of ethanol on the firing rates of Golgi-like neurons and Purkinje neurons in cerebellar slices in vitro. Neurosci Lett 164:9–12PubMedGoogle Scholar
  78. Fritz BM, Grahame NJ, Boehm SL (2012) Selection for high alcohol preference drinking in mice results in heightened sensitivity and rapid development of acute functional tolerance to alcohol’s ataxic effects. Genes Brain Behav 12(1):78–86PubMedPubMedCentralGoogle Scholar
  79. Gallaher EJ, Jones GE, Belknap JK, Crabbe JC (1996) Identification of genetic markers for initial sensitivity and rapid tolerance to ethanol-induced ataxia using quantitative trait locus analysis in BXD recombinant inbred mice. J Pharmacol Exp Ther 277:604–612PubMedGoogle Scholar
  80. Gan G, Guevara A, Marxen M, Neumann M, Junger E, Kobiella A, Mennigen E, Pilhatsch M, Schwarz D, Zimmermann US, Smolka MN (2014) Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex. Biol Psychiatry 76:698–707PubMedPubMedCentralGoogle Scholar
  81. Gatto GJ, McBride WJ, Murphy JM, Lumeng L, Li TK (1994) Ethanol self-infusion into the ventral tegmental area by alcohol-preferring rats. Alcohol 11:557–564PubMedGoogle Scholar
  82. George F, Chu NS (1984) Effects of ethanol on Purkinje cells recorded from cerebellar slices. Alcohol 1:353–358PubMedGoogle Scholar
  83. Gessa GL, Muntoni F, Collu M, Vargiu L, Mereu G (1985) Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Res 348:201–203PubMedGoogle Scholar
  84. Gilman JM, Ramchandani VA, Davis MB, Bjork JM, Hommer DW (2008) Why we like to drink: a functional magnetic resonance imaging study of the rewarding and anxiolytic effects of alcohol. J Neurosci 28:4583–4591PubMedPubMedCentralGoogle Scholar
  85. Glykys J, Mann EO, Mody I (2008) Which GABA(A) receptor subunits are necessary for tonic inhibition in the hippocampus? J Neurosci 28:1421–1426PubMedGoogle Scholar
  86. Grahame NJ, Cunningham CL (1997) Intravenous ethanol self-administration in C57BL/6J and DBA/2J mice. Alcohol Clin Exp Res 21:56–62PubMedGoogle Scholar
  87. Haines DE, May PJ, Dietrichs E (1990) Neuronal connections between the cerebellar nuclei and hypothalamus in Macaca fascicularis: cerebello-visceral circuits. J Comp Neurol 299:106–122PubMedGoogle Scholar
  88. Hamann M, Rossi DJ, Attwell D (2002) Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex. Neuron 33:625–633PubMedGoogle Scholar
  89. Hamlin AS, Newby J, McNally GP (2007) The neural correlates and role of D1 dopamine receptors in renewal of extinguished alcohol-seeking. Neuroscience 146:525–536PubMedGoogle Scholar
  90. Hanchar HJ, Wallner M, Olsen RW (2004) Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic receptors the answer? Life Sci 76:1–8PubMedPubMedCentralGoogle Scholar
  91. Hanchar HJ, Dodson PD, Olsen RW, Otis TS, Wallner M (2005) Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activity. Nat Neurosci 8:339–345PubMedPubMedCentralGoogle Scholar
  92. Hanchar HJ, Chutsrinopkun P, Meera P, Supavilai P, Sieghart W, Wallner M, Olsen RW (2006) Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptors. Proc Natl Acad Sci U S A 103:8546–8551PubMedPubMedCentralGoogle Scholar
  93. Harper JW, Heath RG (1973) Anatomic connections of the fastigial nucleus to the rostral forebrain in the cat. Exp Neurol 39:285–292PubMedPubMedCentralGoogle Scholar
  94. Harris RA, Allan AM, Daniell LC, Nixon C (1988) Antagonism of ethanol and pentobarbital actions by benzodiazepine inverse agonists: neurochemical studies. J Pharmacol Exp Ther 247:1012–1017PubMedPubMedCentralGoogle Scholar
  95. Hasin DS, Stinson FS, Ogburn E, Grant BF (2007) Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on alcohol and related conditions. Arch Gen Psychiatry 64:830–842PubMedGoogle Scholar
  96. Hauser SR, Ding ZM, Getachew B, Toalston JE, Oster SM, McBride WJ, Rodd ZA (2011) The posterior ventral tegmental area mediates alcohol-seeking behavior in alcohol-preferring rats. J Pharmacol Exp Ther 336:857–865PubMedPubMedCentralGoogle Scholar
  97. He Q, Titley H, Grasselli G, Piochon C, Hansel C (2013) Ethanol affects NMDA receptor signaling at climbing fiber-Purkinje cell synapses in mice and impairs cerebellar LTD. J Neurophysiol 109:1333–1342PubMedPubMedCentralGoogle Scholar
  98. Heath RG, Harper JW (1974) Ascending projections of the cerebellar fastigial nucleus to the hippocampus, amygdala, and other temporal lobe sites: evoked potential and histological studies in monkeys and cats. Exp Neurol 45:268–287PubMedPubMedCentralGoogle Scholar
  99. Heath RG, Dempesy CW, Fontana CJ, Myers WA (1978) Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats. Biol Psychiatry 13:501–529PubMedPubMedCentralGoogle Scholar
  100. Heigele S, Sultan S, Toni N, Bischofberger J (2016) Bidirectional GABAergic control of action potential firing in newborn hippocampal granule cells. Nat Neurosci 19:263–270PubMedPubMedCentralGoogle Scholar
  101. Helms CM, Rossi DJ, Grant KA (2012) Neurosteroid influences on sensitivity to ethanol. Front Endocrinol 3:10Google Scholar
  102. Herting MM, Fair D, Nagel BJ (2011) Altered fronto-cerebellar connectivity in alcohol-naive youth with a family history of alcoholism. NeuroImage 54:2582–2589PubMedPubMedCentralGoogle Scholar
  103. Hill SY (2010) Neural plasticity, human genetics, and risk for alcohol dependence. Int Rev Neurobiol 91:53–94PubMedPubMedCentralGoogle Scholar
  104. Hill SY, Muddasani S, Prasad K, Nutche J, Steinhauer SR, Scanlon J, McDermott M, Keshavan M (2007) Cerebellar volume in offspring from multiplex alcohol dependence families. Biol Psychiatry 61:41–47PubMedPubMedCentralGoogle Scholar
  105. Hill SY, Wang S, Carter H, Tessner K, Holmes B, McDermott M, Zezza N, Stiffler S (2011) Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: association with allelic variation in GABRA2 and BDNF. Psychiatry Res 194:304–313PubMedPubMedCentralGoogle Scholar
  106. Hill SY, Lichenstein SD, Wang S, O'Brien J (2016) Volumetric differences in cerebellar lobes in individuals from multiplex alcohol dependence families and controls: their relationship to externalizing and internalizing disorders and working memory. Cerebellum 15:744–754PubMedPubMedCentralGoogle Scholar
  107. Hodge CW, Mehmert KK, Kelley SP, McMahon T, Haywood A, Olive MF, Wang D, Sanchez-Perez AM, Messing RO (1999) Supersensitivity to allosteric GABA(A) receptor modulators and alcohol in mice lacking PKCepsilon. Nat Neurosci 2:997–1002PubMedPubMedCentralGoogle Scholar
  108. Hotson JR (1984) Clinical detection of acute vestibulocerebellar disorders. West J Med 140:910–913PubMedPubMedCentralGoogle Scholar
  109. Huang CM, Huang RH (2007) Ethanol inhibits the sensory responses of cerebellar granule cells in anesthetized cats. Alcohol Clin Exp Res 31:336–344PubMedPubMedCentralGoogle Scholar
  110. Ikai Y, Takada M, Shinonaga Y, Mizuno N (1992) Dopaminergic and non-dopaminergic neurons in the ventral tegmental area of the rat project, respectively, to the cerebellar cortex and deep cerebellar nuclei. Neuroscience 51:719–728PubMedPubMedCentralGoogle Scholar
  111. Ikai Y, Takada M, Mizuno N (1994) Single neurons in the ventral tegmental area that project to both the cerebral and cerebellar cortical areas by way of axon collaterals. Neuroscience 61:925–934PubMedPubMedCentralGoogle Scholar
  112. Inglis FM, Moghaddam B (1999) Dopaminergic innervation of the amygdala is highly responsive to stress. J Neurochem 72:1088–1094PubMedPubMedCentralGoogle Scholar
  113. Ito M (2008) Control of mental activities by internal models in the cerebellum. Nat Rev Neurosci 9:304–313PubMedPubMedCentralGoogle Scholar
  114. Ito M, Yoshida M, Obata K, Kawai N, Udo M (1970) Inhibitory control of intracerebellar nuclei by the purkinje cell axons. Exp Brain Res 10:64–80PubMedPubMedCentralGoogle Scholar
  115. Jahnsen H (1986) Extracellular activation and membrane conductances of neurones in the guinea-pig deep cerebellar nuclei in vitro. J Physiol 372:149–168PubMedPubMedCentralGoogle Scholar
  116. Jensen JP, Nipper MA, Helms ML, Ford MM, Crabbe JC, Rossi DJ, Finn DA (2017) Ethanol withdrawal-induced dysregulation of neurosteroid levels in plasma, cortex, and hippocampus in genetic animal models of high and low withdrawal. Psychopharmacology 234(18):2793–2811PubMedPubMedCentralGoogle Scholar
  117. Jia F, Pignataro L, Harrison NL (2007) GABAA receptors in the thalamus: alpha4 subunit expression and alcohol sensitivity. Alcohol 41:177–185PubMedPubMedCentralGoogle Scholar
  118. Jia F, Chandra D, Homanics GE, Harrison NL (2008) Ethanol modulates synaptic and extrasynaptic GABAA receptors in the thalamus. J Pharmacol Exp Ther 326:475–482PubMedPubMedCentralGoogle Scholar
  119. Jones RM, Lichtenstein P, Grann M, Langstrom N, Fazel S (2011) Alcohol use disorders in schizophrenia: a national cohort study of 12,653 patients. J Clin Psychiatry 72:775–779PubMedPubMedCentralGoogle Scholar
  120. Kakihana R, Brown DR, McClearn GE, Tabershaw IR (1966) Brain sensitivity to alcohol in inbred mouse strains. Science 154:1574–1575PubMedPubMedCentralGoogle Scholar
  121. Kaplan JS, Mohr C, Rossi DJ (2013) Opposite actions of alcohol on tonic GABA(A) receptor currents mediated by nNOS and PKC activity. Nat Neurosci 16:1783–1793PubMedPubMedCentralGoogle Scholar
  122. Kaplan JS, Mohr C, Hostetler CM, Ryabinin AE, Finn DA, Rossi DJ (2016a) Alcohol suppresses tonic GABAA receptor currents in cerebellar granule cells in the prairie vole: a neural signature of high-alcohol-consuming genotypes. Alcohol Clin Exp Res 40:1617–1626PubMedPubMedCentralGoogle Scholar
  123. Kaplan JS, Nipper MA, Richardson BD, Jensen J, Helms M, Finn DA, Rossi DJ (2016b) Pharmacologically counteracting a phenotypic difference in cerebellar GABAA receptor response to alcohol prevents excessive alcohol consumption in a high alcohol-consuming rodent genotype. J Neurosci 36:9019–9025PubMedPubMedCentralGoogle Scholar
  124. Kelly RM, Strick PL (2003) Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci 23:8432–8444PubMedPubMedCentralGoogle Scholar
  125. Kelm MK, Criswell HE, Breese GR (2008) The role of protein kinase A in the ethanol-induced increase in spontaneous GABA release onto cerebellar Purkinje neurons. J Neurophysiol 100:3417–3428PubMedPubMedCentralGoogle Scholar
  126. Kelm MK, Criswell HE, Breese GR (2011) Ethanol-enhanced GABA release: a focus on G protein-coupled receptors. Brain Res Rev 65:113–123PubMedGoogle Scholar
  127. Klemm WR, Stevens RE III (1974) Alcohol effects on EEG and multiple-unit activity in various brain regions of rats. Brain Res 70:361–368PubMedPubMedCentralGoogle Scholar
  128. Klemm WR, Mallari CG, Dreyfus LR, Fiske JC, Forney E, Mikeska JA (1976) Ethanol-induced regional and dose-response differences in multiple-unit activity in rabbits. Psychopharmacology 49:235–244PubMedPubMedCentralGoogle Scholar
  129. Knoflach F, Benke D, Wang Y, Scheurer L, Luddens H, Hamilton BJ, Carter DB, Mohler H, Benson JA (1996) Pharmacological modulation of the diazepam-insensitive recombinant gamma-aminobutyric acidA receptors alpha 4 beta 2 gamma 2 and alpha 6 beta 2 gamma 2. Mol Pharmacol 50:1253–1261PubMedPubMedCentralGoogle Scholar
  130. Koller WC (1983) Alcoholism in essential tremor. Neurology 33:1074–1076PubMedPubMedCentralGoogle Scholar
  131. Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35:217–238PubMedGoogle Scholar
  132. Korpi ER, Debus F, Linden AM, Malecot C, Leppa E, Vekovischeva O, Rabe H, Bohme I, Aller MI, Wisden W, Luddens H (2007) Does ethanol act preferentially via selected brain GABAA receptor subtypes? The current evidence is ambiguous. Alcohol 41:163–176PubMedGoogle Scholar
  133. Koyama S, Brodie MS, Appel SB (2007) Ethanol inhibition of m-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97:1977–1985PubMedGoogle Scholar
  134. Krook-Magnuson E, Szabo GG, Armstrong C, Oijala M, Soltesz I (2014) Cerebellar directed optogenetic intervention inhibits spontaneous hippocampal seizures in a mouse model of temporal lobe epilepsy. eNeuro 1:e.2014. CrossRefPubMedGoogle Scholar
  135. Kumar S, Porcu P, Werner DF, Matthews DB, Diaz-Granados JL, Helfand RS, Morrow AL (2009) The role of GABA(A) receptors in the acute and chronic effects of ethanol: a decade of progress. Psychopharmacology 205:529–564PubMedPubMedCentralGoogle Scholar
  136. Kuo SH, Wang J, Tate WJ, Pan MK, Kelly GC, Gutierrez J, Cortes EP, Vonsattel JG, Louis ED, Faust PL (2017) Cerebellar pathology in early onset and late onset essential tremor. Cerebellum 16:473–482PubMedPubMedCentralGoogle Scholar
  137. Kutlu MG, Gould TJ (2016) Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction. Learn Mem 23:515–533PubMedPubMedCentralGoogle Scholar
  138. Lee S, Yoon BE, Berglund K, Oh SJ, Park H, Shin HS, Augustine GJ, Lee CJ (2010) Channel-mediated tonic GABA release from glia. Science 330:790–796PubMedGoogle Scholar
  139. Levisohn L, Cronin-Golomb A, Schmahmann JD (2000) Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain 123(Pt 5):1041–1050PubMedGoogle Scholar
  140. Lex BW, Lukas SE, Greenwald NE, Mendelson JH (1988) Alcohol-induced changes in body sway in women at risk for alcoholism: a pilot study. J Stud Alcohol 49:346–356PubMedGoogle Scholar
  141. Liang J, Zhang N, Cagetti E, Houser CR, Olsen RW, Spigelman I (2006) Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J Neurosci 26:1749–1758PubMedGoogle Scholar
  142. Liang J, Spigelman I, Olsen RW (2009) Tolerance to sedative/hypnotic actions of GABAergic drugs correlates with tolerance to potentiation of extrasynaptic tonic currents of alcohol-dependent rats. J Neurophysiol 102:224–233PubMedPubMedCentralGoogle Scholar
  143. Lisberger SG, Fuchs AF (1978) Role of primate flocculus during rapid behavioral modification of vestibuloocular reflex. II. Mossy fiber firing patterns during horizontal head rotation and eye movement. J Neurophysiol 41:764–777PubMedGoogle Scholar
  144. Lorenz-Guertin JM, Jacob TC (2017) GABA type a receptor trafficking and the architecture of synaptic inhibition. Dev Neurobiol 78(3):238–270PubMedGoogle Scholar
  145. Loughlin SE, Fallon JH (1983) Dopaminergic and non-dopaminergic projections to amygdala from substantia nigra and ventral tegmental area. Brain Res 262:334–338PubMedGoogle Scholar
  146. Louis ED, Kuo SH, Wang J, Tate WJ, Pan MK, Kelly GC, Gutierrez J, Cortes EP, Vonsattel JG, Faust PL (2017) Cerebellar pathology in familial vs. sporadic essential tremor. Cerebellum 16:786–791PubMedPubMedCentralGoogle Scholar
  147. Luddens H, Pritchett DB, Kohler M, Killisch I, Keinanen K, Monyer H, Sprengel R, Seeburg PH (1990) Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Nature 346:648–651PubMedGoogle Scholar
  148. Mackiewicz Seghete KL, Cservenka A, Herting MM, Nagel BJ (2013) Atypical spatial working memory and task-general brain activity in adolescents with a family history of alcoholism. Alcohol Clin Exp Res 37:390–398PubMedGoogle Scholar
  149. Malila A (1978) Intoxicating effects of three aliphatic alcohols and barbital on two rat strains genetically selected for their ethanol intake. Pharmacol Biochem Behav 8:197–201PubMedGoogle Scholar
  150. Marchant NJ, Hamlin AS, McNally GP (2009) Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking. J Neurosci 29:1331–1342PubMedGoogle Scholar
  151. Marchant NJ, Millan EZ, McNally GP (2012) The hypothalamus and the neurobiology of drug seeking. Cell Mol Life Sci 69:581–597PubMedGoogle Scholar
  152. McCaul ME, Turkkan JS, Svikis DS, Bigelow GE (1991) Familial density of alcoholism: effects on psychophysiological responses to ethanol. Alcohol 8:219–222PubMedGoogle Scholar
  153. McCool BA, Chappell AM (2012) Using monosodium glutamate to initiate ethanol self-administration in inbred mouse strains. Addict Biol 17:121–131PubMedGoogle Scholar
  154. McCool BA, Chappell AM (2014) Persistent enhancement of ethanol drinking following a monosodium glutamate-substitution procedure in C57BL6/J and DBA/2J mice. Alcohol 48:55–61PubMedGoogle Scholar
  155. McDaid J, McElvain MA, Brodie MS (2008) Ethanol effects on dopaminergic ventral tegmental area neurons during block of Ih: involvement of barium-sensitive potassium currents. J Neurophysiol 100:1202–1210PubMedPubMedCentralGoogle Scholar
  156. Meera P, Olsen RW, Otis TS, Wallner M (2010) Alcohol- and alcohol antagonist-sensitive human GABAA receptors: tracking delta subunit incorporation into functional receptors. Mol Pharmacol 78:918–924PubMedPubMedCentralGoogle Scholar
  157. Meera P, Wallner M, Otis TS (2011) Molecular basis for the high THIP/gaboxadol sensitivity of extrasynaptic GABAA receptors. J Neurophysiol 106(4):2057–2064PubMedPubMedCentralGoogle Scholar
  158. Middleton FA, Strick PL (1994) Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science 266:458–461PubMedPubMedCentralGoogle Scholar
  159. Middleton FA, Strick PL (2001) Cerebellar projections to the prefrontal cortex of the primate. J Neurosci 21:700–712PubMedGoogle Scholar
  160. Mihic SJ (1999) Acute effects of ethanol on GABAA and glycine receptor function. Neurochem Int 35:115–123PubMedPubMedCentralGoogle Scholar
  161. Millard WJ (1983) Self-administration of ethanol by genetically heterogeneous mice (RU:NCS): relationship to sensitivity and tolerance. Drug Alcohol Depend 12:333–338PubMedPubMedCentralGoogle Scholar
  162. Mitchell SJ, Silver RA (2003) Shunting inhibition modulates neuronal gain during synaptic excitation. Neuron 38:433–445PubMedGoogle Scholar
  163. Mitchell JM, O’Neil JP, Janabi M, Marks SM, Jagust WJ, Fields HL (2012) Alcohol consumption induces endogenous opioid release in the human orbitofrontal cortex and nucleus accumbens. Sci Transl Med 4:116ra6PubMedPubMedCentralGoogle Scholar
  164. Mitchell JM, O’Neil JP, Jagust WJ, Fields HL (2013) Catechol-O-methyltransferase genotype modulates opioid release in decision circuitry. Clin Transl Sci 6:400–403PubMedPubMedCentralGoogle Scholar
  165. Mittleman G, Goldowitz D, Heck DH, Blaha CD (2008) Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia. Synapse 62:544–550PubMedGoogle Scholar
  166. Mody I (2001) Distinguishing between GABA(A) receptors responsible for tonic and phasic conductances. Neurochem Res 26:907–913PubMedGoogle Scholar
  167. Mody I, Pearce RA (2004) Diversity of inhibitory neurotransmission through GABA(A) receptors. Trends Neurosci 27:569–575PubMedGoogle Scholar
  168. Mohr C, Kolotushkina O, Kaplan JS, Welsh J, Daunais JB, Grant KA, Rossi DJ (2013) Primate cerebellar granule cells exhibit a tonic GABAAR conductance that is not affected by alcohol: a possible cellular substrate of the low level of response phenotype. Front Neural Circuits 7:189PubMedPubMedCentralGoogle Scholar
  169. Moldavan MG, Cravetchi O, Allen CN (2017) GABA transporters regulate tonic and synaptic GABAA receptor-mediated currents in the Suprachiasmatic nucleus neurons. J Neurophysiol 118(6):3092–3106PubMedPubMedCentralGoogle Scholar
  170. Monaghan PL, Beitz AJ, Larson AA, Altschuler RA, Madl JE, Mullett MA (1986) Immunocytochemical localization of glutamate-, glutaminase- and aspartate aminotransferase-like immunoreactivity in the rat deep cerebellar nuclei. Brain Res 363:364–370PubMedGoogle Scholar
  171. Moore EM, Serio KM, Goldfarb KJ, Stepanovska S, Linsenbardt DN, Boehm SL (2007) GABAergic modulation of binge-like ethanol intake in C57BL/6J mice. Pharmacol Biochem Behav 88:105–113PubMedPubMedCentralGoogle Scholar
  172. Morikawa H, Morrisett RA (2010) Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction with intrinsic ion channels and neurotransmitter inputs. Int Rev Neurobiol 91:235–288PubMedPubMedCentralGoogle Scholar
  173. Mostile G, Jankovic J (2010) Alcohol in essential tremor and other movement disorders. Mov Disord 25:2274–2284PubMedGoogle Scholar
  174. Mothersill O, Knee-Zaska C, Donohoe G (2015) Emotion and theory of mind in schizophrenia-investigating the role of the cerebellum. Cerebellum 15(3):357–368Google Scholar
  175. Mrejeru A, Marti-Prats L, Avegno EM, Harrison NL, Sulzer D (2015) A subset of ventral tegmental area dopamine neurons responds to acute ethanol. Neuroscience 290:649–658PubMedPubMedCentralGoogle Scholar
  176. Mulder MJ, Baeyens D, Davidson MC, Casey BJ, van den BE, van Engeland H, Durston S (2008) Familial vulnerability to ADHD affects activity in the cerebellum in addition to the prefrontal systems. J Am Acad Child Adolesc Psychiatry 47:68–75PubMedPubMedCentralGoogle Scholar
  177. Newlin DB, Renton RM (2010) High risk groups often have higher levels of alcohol response than low risk: the other side of the coin. Alcohol Clin Exp Res 34:199–202PubMedPubMedCentralGoogle Scholar
  178. Newlin DB, Thomson JB (1990) Alcohol challenge with sons of alcoholics: a critical review and analysis. Psychol Bull 108:383–402PubMedPubMedCentralGoogle Scholar
  179. Newman PP, Reza H (1979) Functional relationships between the hippocampus and the cerebellum: an electrophysiological study of the cat. J Physiol 287:405–426PubMedPubMedCentralGoogle Scholar
  180. Nie Z, Madamba SG, Siggins GR (1994) Ethanol inhibits glutamatergic neurotransmission in nucleus accumbens neurons by multiple mechanisms. J Pharmacol Exp Ther 271:1566–1573PubMedPubMedCentralGoogle Scholar
  181. Nie Z, Madamba SG, Siggins GR (2000) Ethanol enhances gamma-aminobutyric acid responses in a subpopulation of nucleus accumbens neurons: role of metabotropic glutamate receptors. J Pharmacol Exp Ther 293:654–661PubMedPubMedCentralGoogle Scholar
  182. Nie Z, Zorrilla EP, Madamba SG, Rice KC, Roberto M, Siggins GR (2009) Presynaptic CRF1 receptors mediate the ethanol enhancement of GABAergic transmission in the mouse central amygdala. Sci World J 9:68–85Google Scholar
  183. Nie H, Rewal M, Gill TM, Ron D, Janak PH (2011) Extrasynaptic delta-containing GABAA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake. Proc Natl Acad Sci U S A 108:4459–4464PubMedPubMedCentralGoogle Scholar
  184. Nikolaou K, Critchley H, Duka T (2013a) Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response. PLoS One 8:e76649PubMedPubMedCentralGoogle Scholar
  185. Nikolaou K, Field M, Critchley H, Duka T (2013b) Acute alcohol effects on attentional bias are mediated by subcortical areas associated with arousal and salience attribution. Neuropsychopharmacology 38:1365–1373PubMedPubMedCentralGoogle Scholar
  186. Nowak KL, McBride WJ, Lumeng L, Li TK, Murphy JM (1998) Blocking GABA(A) receptors in the anterior ventral tegmental area attenuates ethanol intake of the alcohol-preferring P rat. Psychopharmacology 139:108–116PubMedPubMedCentralGoogle Scholar
  187. Oades RD, Halliday GM (1987) Ventral tegmental (A10) system: neurobiology. 1. Anatomy and connectivity. Brain Res 434:117–165PubMedPubMedCentralGoogle Scholar
  188. Okamoto T, Harnett MT, Morikawa H (2006) Hyperpolarization-activated cation current (Ih) is an ethanol target in midbrain dopamine neurons of mice. J Neurophysiol 95:619–626PubMedGoogle Scholar
  189. Olsen RW, Hanchar HJ, Meera P, Wallner M (2007) GABAA receptor subtypes: the “one glass of wine” receptors. Alcohol 41:201–209PubMedPubMedCentralGoogle Scholar
  190. Ostroumov A, Thomas AM, Kimmey BA, Karsch JS, Doyon WM, Dani JA (2016) Stress increases ethanol self-administration via a shift toward excitatory GABA signaling in the ventral tegmental area. Neuron 92:493–504PubMedPubMedCentralGoogle Scholar
  191. Palmer MR, Sorensen SM, Freedman R, Olson L, Hoffer B, Seiger A (1982) Differential ethanol sensitivity of intraocular cerebellar grafts in long-sleep and short-sleep mice. J Pharmacol Exp Ther 222:480–487PubMedPubMedCentralGoogle Scholar
  192. Palmer MR, Basile AS, Proctor WR, Baker RC, Dunwiddie TV (1985) Ethanol tolerance of cerebellar purkinje neurons from selectively outbred mouse lines: in vivo and in vitro electrophysiological investigations. Alcohol Clin Exp Res 9:291–296PubMedPubMedCentralGoogle Scholar
  193. Palmer MR, van Horne CG, Harlan JT, Moore EA (1988) Antagonism of ethanol effects on cerebellar Purkinje neurons by the benzodiazepine inverse agonists Ro 15-4513 and FG 7142: electrophysiological studies. J Pharmacol Exp Ther 247:1018–1024PubMedPubMedCentralGoogle Scholar
  194. Park HM, Choi IS, Nakamura M, Cho JH, Lee MG, Jang IS (2011) Multiple effects of allopregnanolone on GABAergic responses in single hippocampal CA3 pyramidal neurons. Eur J Pharmacol 652:46–54PubMedPubMedCentralGoogle Scholar
  195. Paulus KS, Magnano I, Conti M, Galistu P, D'Onofrio M, Satta W, Aiello I (2004) Pure post-stroke cerebellar cognitive affective syndrome: a case report. Neurol Sci 25:220–224PubMedPubMedCentralGoogle Scholar
  196. Perciavalle V, Berretta S, Raffaele R (1989) Projections from the intracerebellar nuclei to the ventral midbrain tegmentum in the rat. Neuroscience 29:109–119PubMedPubMedCentralGoogle Scholar
  197. Peris J, Coleman-Hardee M, Burry J, Pecins-Thompson M (1992) Selective changes in GABAergic transmission in substantia nigra and superior colliculus caused by ethanol and ethanol withdrawal. Alcohol Clin Exp Res 16:311–319PubMedGoogle Scholar
  198. Phillips TJ, Reed C (2014) Targeting GABAB receptors for anti-abuse drug discovery. Expert Opin Drug Discovery 9:1307–1317Google Scholar
  199. Pina MM, Young EA, Ryabinin AE, Cunningham CL (2015) The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice. Neuropharmacology 99:627–638PubMedPubMedCentralGoogle Scholar
  200. Pirker S, Schwarzer C, Wieselthaler A, Sieghart W, Sperk G (2000) GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience 101:815–850PubMedPubMedCentralGoogle Scholar
  201. Ponomarev I, Crabbe JC (2002) A novel method to assess initial sensitivity and acute functional tolerance to hypnotic effects of ethanol. J Pharmacol Exp Ther 302:257–263PubMedPubMedCentralGoogle Scholar
  202. Porcu P, Morrow AL (2014) Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: relevance for human studies. Psychopharmacology 231:3257–3272PubMedPubMedCentralGoogle Scholar
  203. Pugh JR, Jahr CE (2011) Axonal GABAA receptors increase cerebellar granule cell excitability and synaptic activity. J Neurosci 31:565–574PubMedPubMedCentralGoogle Scholar
  204. Pugh JR, Jahr CE (2013) Activation of axonal receptors by GABA spillover increases somatic firing. J Neurosci 33:16924–16929PubMedPubMedCentralGoogle Scholar
  205. Qi ZH, Song M, Wallace MJ, Wang D, Newton PM, McMahon T, Chou WH, Zhang C, Shokat KM, Messing RO (2007) Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits. J Biol Chem 282:33052–33063PubMedPubMedCentralGoogle Scholar
  206. Quinn PD, Fromme K (2011) Subjective response to alcohol challenge: a quantitative review. Alcohol Clin Exp Res 35:1759–1770PubMedPubMedCentralGoogle Scholar
  207. Ragge NK, Hartley C, Dearlove AM, Walker J, Russell-Eggitt I, Harris CM (2003) Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new nystagmus locus. J Med Genet 40:37–41PubMedPubMedCentralGoogle Scholar
  208. Ramaker MJ, Ford MM, Fretwell AM, Finn DA (2011) Alteration of ethanol drinking in mice via modulation of the GABA(A) receptor with ganaxolone, finasteride, and gaboxadol. Alcohol Clin Exp Res 35(11):1994–2007PubMedPubMedCentralGoogle Scholar
  209. Ramaker MJ, Strong MN, Ford MM, Finn DA (2012) Effect of ganaxolone and THIP on operant and limited-access ethanol self-administration. Neuropharmacology 63:555–564PubMedPubMedCentralGoogle Scholar
  210. Ramaker MJ, Strong-Kaufman MN, Ford MM, Phillips TJ, Finn DA (2015) Effect of nucleus accumbens shell infusions of ganaxolone or gaboxadol on ethanol consumption in mice. Psychopharmacology 232:1415–1426PubMedPubMedCentralGoogle Scholar
  211. Rautakorpi I, Marttila RJ, Rinne UK (1983) Alcohol consumption of patients with essential tremor. Acta Neurol Scand 68:177–179PubMedPubMedCentralGoogle Scholar
  212. Reilly MT, Milner LC, Shirley RL, Crabbe JC, Buck KJ (2008) 5-HT2C and GABAB receptors influence handling-induced convulsion severity in chromosome 4 congenic and DBA/2J background strain mice. Brain Res 1198:124–131PubMedPubMedCentralGoogle Scholar
  213. Rewal M, Jurd R, Gill TM, He DY, Ron D, Janak PH (2009) Alpha4-containing GABAA receptors in the nucleus accumbens mediate moderate intake of alcohol. J Neurosci 29:543–549PubMedPubMedCentralGoogle Scholar
  214. Rewal M, Donahue R, Gill TM, Nie H, Ron D, Janak PH (2012) Alpha4 subunit-containing GABAA receptors in the accumbens shell contribute to the reinforcing effects of alcohol. Addict Biol 17:309–321PubMedGoogle Scholar
  215. Richardson BD, Rossi DJ (2017) Recreational concentrations of alcohol enhance synaptic inhibition of cerebellar unipolar brush cells via pre- and postsynaptic mechanisms. J Neurophysiol 118:267–279PubMedPubMedCentralGoogle Scholar
  216. Richardson BD, Ling LL, Uteshev VV, Caspary DM (2011) Extrasynaptic GABA(A) receptors and tonic inhibition in rat auditory thalamus. PLoS One 6:e16508PubMedPubMedCentralGoogle Scholar
  217. Riley EP, Worsham ED, Lester D, Freed EX (1977) Selective breeding of rats for differences in reactivity to alcohol. An approach to an animal model of alcoholism. II. Behavioral measures. J Stud Alcohol 38:1705–1717PubMedPubMedCentralGoogle Scholar
  218. Roberto M, Madamba SG, Moore SD, Tallent MK, Siggins GR (2003) Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons. Proc Natl Acad Sci U S A 100:2053–2058PubMedPubMedCentralGoogle Scholar
  219. Rochefort C, Arabo A, Andre M, Poucet B, Save E, Rondi-Reig L (2011) Cerebellum shapes hippocampal spatial code. Science 334:385–389PubMedPubMedCentralGoogle Scholar
  220. Rodd ZA, Bell RL, Zhang Y, Murphy JM, Goldstein A, Zaffaroni A, Li TK, McBride WJ (2005) Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: involvement of dopamine and serotonin. Neuropsychopharmacology 30:330–338PubMedPubMedCentralGoogle Scholar
  221. Rodd-Henricks ZA, McKinzie DL, Crile RS, Murphy JM, McBride WJ (2000) Regional heterogeneity for the intracranial self-administration of ethanol within the ventral tegmental area of female Wistar rats. Psychopharmacology 149:217–224PubMedPubMedCentralGoogle Scholar
  222. Rogers J, Siggins GR, Schulman JA, Bloom FE (1980) Physiological correlates of ethanol intoxication tolerance, and dependence in rat cerebellar Purkinje cells. Brain Res 196:183–198PubMedPubMedCentralGoogle Scholar
  223. Rogers TD, Dickson PE, Heck DH, Goldowitz D, Mittleman G, Blaha CD (2011) Connecting the dots of the cerebro-cerebellar role in cognitive function: neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex. Synapse 65:1204–1212PubMedPubMedCentralGoogle Scholar
  224. Rogers TD, Dickson PE, McKimm E, Heck DH, Goldowitz D, Blaha CD, Mittleman G (2013) Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder. Cerebellum 12:547–556PubMedPubMedCentralGoogle Scholar
  225. Rossi DJ, Hamann M (1998) Spillover-mediated transmission at inhibitory synapses promoted by high affinity alpha6 subunit GABA(A) receptors and glomerular geometry. Neuron 20:783–795PubMedPubMedCentralGoogle Scholar
  226. Rossi DJ, Hamann M, Attwell D (2003) Multiple modes of GABAergic inhibition of rat cerebellar granule cells. J Physiol 548:97–110PubMedPubMedCentralGoogle Scholar
  227. Santhakumar V, Wallner M, Otis TS (2007) Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition. Alcohol 41:211–221PubMedPubMedCentralGoogle Scholar
  228. Santhakumar V, Meera P, Karakossian MH, Otis TS (2013) A reinforcing circuit action of extrasynaptic GABAA receptor modulators on cerebellar granule cell inhibition. PLoS One 8:e72976PubMedPubMedCentralGoogle Scholar
  229. Sasaki K, Jinnai K, Gemba H, Hashimoto S, Mizuno N (1979) Projection of the cerebellar dentate nucleus onto the frontal association cortex in monkeys. Exp Brain Res 37:193–198PubMedPubMedCentralGoogle Scholar
  230. Schmahmann JD (2004) Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 16:367–378PubMedPubMedCentralGoogle Scholar
  231. Schmahmann JD (2010) The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev 20:236–260PubMedPubMedCentralGoogle Scholar
  232. Schmahmann JD, Caplan D (2006) Cognition, emotion and the cerebellum. Brain 129:290–292PubMedPubMedCentralGoogle Scholar
  233. Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121(Pt 4):561–579PubMedPubMedCentralGoogle Scholar
  234. Schmahmann JD, MacMore J, Vangel M (2009) Cerebellar stroke without motor deficit: clinical evidence for motor and non-motor domains within the human cerebellum. Neuroscience 162:852–861PubMedPubMedCentralGoogle Scholar
  235. Schneider F, Habel U, Wagner M, Franke P, Salloum JB, Shah NJ, Toni I, Sulzbach C, Honig K, Maier W, Gaebel W, Zilles K (2001) Subcortical correlates of craving in recently abstinent alcoholic patients. Am J Psychiatry 158:1075–1083PubMedPubMedCentralGoogle Scholar
  236. Schousboe A, Madsen KK, Barker-Haliski ML, White HS (2014) The GABA synapse as a target for antiepileptic drugs: a historical overview focused on GABA transporters. Neurochem Res 39:1980–1987PubMedPubMedCentralGoogle Scholar
  237. Schraa-Tam CK, Rietdijk WJ, Verbeke WJ, Dietvorst RC, van den Berg WE, Bagozzi RP, De Zeeuw CI (2012) fMRI activities in the emotional cerebellum: a preference for negative stimuli and goal-directed behavior. Cerebellum 11:233–245PubMedPubMedCentralGoogle Scholar
  238. Schroeder D, Nasrallah HA (1982) High alcoholism rate in patients with essential tremor. Am J Psychiatry 139:1471–1473PubMedPubMedCentralGoogle Scholar
  239. Schuckit MA (1985) Ethanol-induced changes in body sway in men at high alcoholism risk. Arch Gen Psychiatry 42:375–379PubMedPubMedCentralGoogle Scholar
  240. Schuckit MA, Smith TL (1996) An 8-year follow-up of 450 sons of alcoholic and control subjects. Arch Gen Psychiatry 53:202–210PubMedPubMedCentralGoogle Scholar
  241. Schuckit MA, Tsuang JW, Anthenelli RM, Tipp JE, Nurnberger JI Jr (1996) Alcohol challenges in young men from alcoholic pedigrees and control families: a report from the COGA project. J Stud Alcohol 57:368–377PubMedPubMedCentralGoogle Scholar
  242. Schuckit MA, Smith TL, Danko GP, Isacescu V (2003) Level of response to alcohol measured on the self-rating of the effects of alcohol questionnaire in a group of 40-year-old women. Am J Drug Alcohol Abuse 29:191–201PubMedPubMedCentralGoogle Scholar
  243. Schuckit MA, Smith TL, Kalmijn J, Danko GP (2005) A cross-generational comparison of alcohol challenges at about age 20 in 40 father-offspring pairs. Alcohol Clin Exp Res 29:1921–1927PubMedPubMedCentralGoogle Scholar
  244. Schuckit MA, Smith TL, Trim RS, Heron J, Horwood J, Davis J, Hibbeln J (2008) The self-rating of the effects of alcohol questionnaire as a predictor of alcohol-related outcomes in 12-year-old subjects. Alcohol Alcohol 43:641–646PubMedPubMedCentralGoogle Scholar
  245. Schuckit MA, Smith TL, Trim RS, Allen RC, Fukukura T, Knight EE, Cesario EM, Kreikebaum SA (2011) A prospective evaluation of how a low level of response to alcohol predicts later heavy drinking and alcohol problems. Am J Drug Alcohol Abuse 37:479–486PubMedPubMedCentralGoogle Scholar
  246. Sharma VK, Hill SY (2017) Differentiating the effects of familial risk for alcohol dependence and prenatal exposure to alcohol on offspring brain morphology. Alcohol Clin Exp Res 41:312–322PubMedPubMedCentralGoogle Scholar
  247. Siggins GR, French E (1979) Central neurons are depressed by iontophoretic and micropressure application of ethanol and tetrahydropapaveroline. Drug Alcohol Depend 4:239–243PubMedPubMedCentralGoogle Scholar
  248. Silberman Y, Ariwodola OJ, Weiner JL (2009) Differential effects of GABAB autoreceptor activation on ethanol potentiation of local and lateral paracapsular GABAergic synapses in the rat basolateral amygdala. Neuropharmacology 56:886–895PubMedPubMedCentralGoogle Scholar
  249. Snelling C, Tanchuck-Nipper MA, Ford MM, Jensen JP, Cozzoli DK, Ramaker MJ, Helms M, Crabbe JC, Rossi DJ, Finn DA (2014) Quantification of ten neuroactive steroids in plasma in withdrawal seizure-prone and -resistant mice during chronic ethanol withdrawal. Psychopharmacology 231:3401–3414PubMedPubMedCentralGoogle Scholar
  250. Sorensen S, Palmer M, Dunwiddie T, Hoffer B (1980) Electrophysiological correlates of ethanol-induced sedation in differentially sensitive lines of mice. Science 210:1143–1145PubMedPubMedCentralGoogle Scholar
  251. Sorensen S, Dunwiddie T, McClearn G, Freedman R, Hoffer B (1981) Ethanol-induced depressions in cerebellar and hippocampal neurons of mice selectively bred for differences in ethanol sensitivity: an electrophysiological study. Pharmacol Biochem Behav 14:227–234PubMedPubMedCentralGoogle Scholar
  252. Spanagel R (2009) Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev 89:649–705PubMedGoogle Scholar
  253. Spuhler K, Deitrich RA (1984) Correlative analysis of ethanol-related phenotypes in rat inbred strains. Alcohol Clin Exp Res 8:480–484PubMedGoogle Scholar
  254. Steffensen SC, Walton CH, Hansen DM, Yorgason JT, Gallegos RA, Criado JR (2009) Contingent and non-contingent effects of low-dose ethanol on GABA neuron activity in the ventral tegmental area. Pharmacol Biochem Behav 92:68–75PubMedGoogle Scholar
  255. Stell BM, Mody I (2002) Receptors with different affinities mediate phasic and tonic GABA(A) conductances in hippocampal neurons. J Neurosci 22:RC223PubMedGoogle Scholar
  256. Stell BM, Brickley SG, Tang CY, Farrant M, Mody I (2003) Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proc Natl Acad Sci U S A 100:14439–14444PubMedPubMedCentralGoogle Scholar
  257. Stobbs SH, Ohran AJ, Lassen MB, Allison DW, Brown JE, Steffensen SC (2004) Ethanol suppression of ventral tegmental area GABA neuron electrical transmission involves N-methyl-D-aspartate receptors. J Pharmacol Exp Ther 311:282–289PubMedGoogle Scholar
  258. Stoodley CJ, Schmahmann JD (2009) Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. NeuroImage 44:489–501PubMedGoogle Scholar
  259. Stoodley CJ, Schmahmann JD (2010) Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 46:831–844PubMedPubMedCentralGoogle Scholar
  260. Stoodley CJ, Valera EM, Schmahmann JD (2010) An fMRI study of intra-individual functional topography in the human cerebellum. Behav Neurol 23:65–79PubMedPubMedCentralGoogle Scholar
  261. Stoodley CJ, Valera EM, Schmahmann JD (2012) Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. NeuroImage 59:1560–1570PubMedGoogle Scholar
  262. Strick PL, Dum RP, Fiez JA (2009) Cerebellum and nonmotor function. Annu Rev Neurosci 32:413–434PubMedGoogle Scholar
  263. Tabakoff B, Kiianmaa K (1982) Does tolerance develop to the activating, as well as the depressant, effects of ethanol? Pharmacol Biochem Behav 17:1073–1076PubMedGoogle Scholar
  264. Tavano A, Grasso R, Gagliardi C, Triulzi F, Bresolin N, Fabbro F, Borgatti R (2007) Disorders of cognitive and affective development in cerebellar malformations. Brain 130:2646–2660PubMedPubMedCentralGoogle Scholar
  265. ten Bruggencate G, Teichmann R, Weller E (1972) Neuronal activity in the lateral vestibular nucleus of the cat. 3. Inhibitory actions of cerebellar Purkinje cells evoked via mossy and climbing fibre afferents. Pflugers Arch 337:147–162PubMedGoogle Scholar
  266. Teune TM, van der Burg J, De Zeeuw CI, Voogd J, Ruigrok TJ (1998) Single Purkinje cell can innervate multiple classes of projection neurons in the cerebellar nuclei of the rat: a light microscopic and ultrastructural triple-tracer study in the rat. J Comp Neurol 392:164–178PubMedGoogle Scholar
  267. Thach WT (1968) Discharge of Purkinje and cerebellar nuclear neurons during rapidly alternating arm movements in the monkey. J Neurophysiol 31:785–797PubMedGoogle Scholar
  268. Thach WT (1970) Discharge of cerebellar neurons related to two maintained postures and two prompt movements. II. Purkinje cell output and input. J Neurophysiol 33:537–547PubMedGoogle Scholar
  269. Theile JW, Morikawa H, Gonzales RA, Morrisett RA (2008) Ethanol enhances GABAergic transmission onto dopamine neurons in the ventral tegmental area of the rat. Alcohol Clin Exp Res 32:1040–1048PubMedPubMedCentralGoogle Scholar
  270. Theile JW, Morikawa H, Gonzales RA, Morrisett RA (2009) Role of 5-hydroxytryptamine2C receptors in Ca2+-dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons. J Pharmacol Exp Ther 329:625–633PubMedPubMedCentralGoogle Scholar
  271. Theile JW, Morikawa H, Gonzales RA, Morrisett RA (2011) GABAergic transmission modulates ethanol excitation of ventral tegmental area dopamine neurons. Neuroscience 172:94–103PubMedGoogle Scholar
  272. Tomasi D, Volkow ND (2011) Association between functional connectivity hubs and brain networks. Cereb Cortex 21:2003–2013PubMedPubMedCentralGoogle Scholar
  273. Trudell JR, Messing RO, Mayfield J, Harris RA (2014) Alcohol dependence: molecular and behavioral evidence. Trends Pharmacol Sci 35:317–323PubMedPubMedCentralGoogle Scholar
  274. Tyzio R, Cossart R, Khalilov I, Minlebaev M, Hubner CA, Represa A, Ben-Ari Y, Khazipov R (2006) Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 314:1788–1792PubMedGoogle Scholar
  275. Valenzuela CF, Jotty K (2015) Mini-review: effects of ethanol on GABAA receptor-mediated neurotransmission in the cerebellar cortex – recent advances. Cerebellum 14:438–446PubMedGoogle Scholar
  276. Varagic Z, Ramerstorfer J, Huang S, Rallapalli S, Sarto-Jackson I, Cook J, Sieghart W, Ernst M (2013) Subtype selectivity of alpha+beta-site ligands of GABAA receptors: identification of the first highly specific positive modulators at alpha6beta2/3gamma2 receptors. Br J Pharmacol 169:384–399PubMedPubMedCentralGoogle Scholar
  277. Volkow ND, Ma Y, Zhu W, Fowler JS, Li J, Rao M, Mueller K, Pradhan K, Wong C, Wang GJ (2008) Moderate doses of alcohol disrupt the functional organization of the human brain. Psychiatry Res 162:205–213PubMedPubMedCentralGoogle Scholar
  278. Wadiche JI, Jahr CE (2005) Patterned expression of Purkinje cell glutamate transporters controls synaptic plasticity. Nat Neurosci 8:1329–1334PubMedGoogle Scholar
  279. Wagner MJ, Kim TH, Savall J, Schnitzer MJ, Luo L (2017) Cerebellar granule cells encode the expectation of reward. Nature 544:96–100PubMedPubMedCentralGoogle Scholar
  280. Wall MJ, Usowicz MM (1997) Development of action potential-dependent and independent spontaneous GABAA receptor-mediated currents in granule cells of postnatal rat cerebellum. Eur J Neurosci 9:533–548PubMedPubMedCentralGoogle Scholar
  281. Wallner M, Hanchar HJ, Olsen RW (2003) Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc Natl Acad Sci U S A 100:15218–15223PubMedPubMedCentralGoogle Scholar
  282. Watson TC, Becker N, Apps R, Jones MW (2014) Back to front: cerebellar connections and interactions with the prefrontal cortex. Front Syst Neurosci 8:4PubMedPubMedCentralGoogle Scholar
  283. Weber AM, Soreni N, Noseworthy MD (2014) A preliminary study on the effects of acute ethanol ingestion on default mode network and temporal fractal properties of the brain. MAGMA 27:291–301PubMedGoogle Scholar
  284. Wegelius K, Honkanen A, Korpi ER (1994) Benzodiazepine receptor ligands modulate ethanol drinking in alcohol-preferring rats. Eur J Pharmacol 263:141–147PubMedGoogle Scholar
  285. Weitlauf C, Woodward JJ (2008) Ethanol selectively attenuates NMDAR-mediated synaptic transmission in the prefrontal cortex. Alcohol Clin Exp Res 32:690–698PubMedPubMedCentralGoogle Scholar
  286. Welsh JP, Yuen G, Placantonakis DG, Vu TQ, Haiss F, O'Hearn E, Molliver ME, Aicher SA (2002) Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4, and the cerebellar contribution to posthypoxic myoclonus. Adv Neurol 89:331–359PubMedGoogle Scholar
  287. Welsh JP, Han VZ, Rossi DJ, Mohr C, Odagiri M, Daunais JB, Grant KA (2011) Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence. Proc Natl Acad Sci U S A 108:10314–10319PubMedPubMedCentralGoogle Scholar
  288. Wolf U, Rapoport MJ, Schweizer TA (2009) Evaluating the affective component of the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 21:245–253PubMedGoogle Scholar
  289. Xiao C, Shao XM, Olive MF, Griffin WC III, Li KY, Krnjevic K, Zhou C, Ye JH (2009) Ethanol facilitates glutamatergic transmission to dopamine neurons in the ventral tegmental area. Neuropsychopharmacology 34:307–318PubMedGoogle Scholar
  290. Yang X, Criswell HE, Breese GR (2000) Ethanol modulation of gamma-aminobutyric acid (GABA)-mediated inhibition of cerebellar Purkinje neurons: relationship to GABAb receptor input. Alcohol Clin Exp Res 24:682–690PubMedGoogle Scholar
  291. Ye Z, McGee TP, Houston CM, Brickley SG (2013) The contribution of delta subunit-containing GABAA receptors to phasic and tonic conductance changes in cerebellum, thalamus and neocortex. Front Neural Circuits 7:203PubMedPubMedCentralGoogle Scholar
  292. Yoneyama N, Crabbe JC, Ford MM, Murillo A, Finn DA (2008) Voluntary ethanol consumption in 22 inbred mouse strains. Alcohol 42:149–160PubMedPubMedCentralGoogle Scholar
  293. Yu W, Krook-Magnuson E (2015) Cognitive collaborations: bidirectional functional connectivity between the cerebellum and the hippocampus. Front Syst Neurosci 9:177PubMedPubMedCentralGoogle Scholar
  294. Zamudio-Bulcock PA, Homanics GE, Woodward JJ (2018) Loss of ethanol inhibition of NMDAR-mediated currents and plasticity of cerebellar synapses in mice expressing the GluN1(F639A) subunit. Alcohol Clin Exp Res.
  295. Zhang XY, Wang JJ, Zhu JN (2016) Cerebellar fastigial nucleus: from anatomic construction to physiological functions. Cerebellum Ataxias 3:9PubMedPubMedCentralGoogle Scholar
  296. Zhu JN, Wang JJ (2008) The cerebellum in feeding control: possible function and mechanism. Cell Mol Neurobiol 28:469–478PubMedPubMedCentralGoogle Scholar
  297. Zhu JN, Yung WH, Kwok-Chong CB, Chan YS, Wang JJ (2006) The cerebellar-hypothalamic circuits: potential pathways underlying cerebellar involvement in somatic-visceral integration. Brain Res Rev 52:93–106PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Integrative Physiology and NeuroscienceCollege of Veterinary Medicine, Washington State UniversityPullmanUSA
  2. 2.Alcohol and Drug Abuse Research ProgramWashington State UniversityPullmanUSA
  3. 3.Department of Biological EngineeringUniversity of IdahoMoscowUSA

Personalised recommendations