title: Repeated binge-like ethanol drinking alters ethanol drinking patterns and depresses striatal GABAergic transmission.
abstract: Repeated cycles of binge alcohol drinking and abstinence are key components in the development of dependence. However, the precise behavioral mechanisms underlying binge-like drinking and its consequences on striatal synaptic physiology remain unclear. In the present study, ethanol and water drinking patterns were recorded with high temporal resolution over 6 weeks of binge-like ethanol drinking using the 'drinking in the dark' (DID) protocol. The bottle exchange occurring at the beginning of each session prompted a transient increase in the drinking rate that might facilitate the acquisition of ethanol binge-like drinking. Ethanol drinking mice also displayed a 'front-loading' behavior, in which the highest rate of drinking was recorded during the first 15 min. This rate increased over weeks and paralleled the mild escalation of blood ethanol concentrations. GABAergic and glutamatergic transmission in the dorsal striatum were examined following DID. Spontaneous glutamatergic transmission and the density of dendritic spines were unchanged after ethanol drinking. However, the frequency of GABAA receptor-mediated inhibitory postsynaptic currents was depressed in medium spiny neurons of ethanol drinking mice. A history of ethanol drinking also increased ethanol preference and altered the acute ethanol effects on GABAergic transmission differentially in dorsolateral and dorsomedial striatum. Together, the study shows that the bottle exchange during DID promotes fast, voluntary ethanol drinking and that this intermittent pattern of ethanol drinking causes a depression of GABAergic transmission in the dorsal striatum.
authors.affiliation: Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Wilcox
authors.affiliation: Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Verginia C
authors.initials: VC
authors.lastname: Cuzon Carlson
authors.affiliation: Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Nyssa
authors.initials: N
authors.lastname: Sherazee
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Sprow
authors.affiliation: Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Bock
authors.affiliation: 1] Department of Psychology, University of North Carolina, Chapel Hill, NC, USA [2] Bowles Center for Alcohol Studies, University of North Carolina, Bethesda, MD, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Thiele
authors.affiliation: Section on Synaptic Pharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
authors.affiliation: Section on Neuronal Structure, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Alvarez
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D002755:Choice Behavior / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000648:ultrastructure; D010852:Picrotoxin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D018756:GABA Antagonists; D018698:Glutamic Acid; D010852:Picrotoxin