title: Effects of vigabatrin, an irreversible GABA transaminase inhibitor, on ethanol reinforcement and ethanol discriminative stimuli in mice.
abstract: We tested the hypothesis that the irreversible γ-amino butyric acid transaminase inhibitor, γ-vinyl γ-amino butyric acid [vigabatrin (VGB)], would reduce ethanol reinforcement and enhance the discriminative-stimulus effect of ethanol, effectively reducing ethanol intake. The present studies used adult C57BL/6J (B6) mice in well-established operant, two-bottle choice consumption, locomotor activity, and ethanol discrimination procedures to comprehensively examine the effects of VGB on ethanol-supported behaviors. VGB dose-dependently reduced operant responding for ethanol and ethanol consumption for long periods of time. Importantly, a low dose (200 mg/kg) of VGB was selective for reducing ethanol responding without altering the intake of food or water reinforcement. Higher VGB doses (>200mg/kg) reduced ethanol intake, but also significantly increased water consumption and, more modestly, increased food consumption. Although not affecting locomotor activity on its own, VGB interacted with ethanol to reduce the stimulatory effects of ethanol on locomotion. Finally, VGB (200 mg/kg) significantly enhanced the discriminative-stimulus effects of ethanol as evidenced by significant leftward and upward shifts in ethanol generalization curves. Interestingly, VGB treatment was associated with slight increases in blood ethanol concentrations. The reduction in ethanol intake by VGB appears to be related to the ability of VGB to potentiate the pharmacological effects of ethanol.
authors.affiliation: Charleston Alcohol Research Center, Department of Psychiatry & Behavioral Science, Medical University of South Carolina, South Carolina 29425, USA. griffinw@musc.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Griffin
authors.forename: Shaun A
authors.initials: SA
authors.lastname: Nguyen
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Deleon
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Middaugh
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000819:agonists* / Q000097:blood / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration; D020888:Vigabatrin / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D000431:Ethanol; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin