title: Alterations in the rate of binge ethanol consumption:  implications for preclinical studies in mice.
abstract: The rate at which alcohol (ethanol) is consumed has direct impact on its behavioral and subjective effects. For this reason, alterations in the pattern of ethanol consumption as a function of drinking history might be critical to the development and maintenance of alcoholism. Furthermore, because pharmacological interventions aimed at disrupting the motivation to consume ethanol are dependent on the brain/plasma concentrations present when an individual is most likely to engage in consumption of this substance, characterizing temporal drinking patterns might be useful to determine the timing of such treatments. The primary goal of the present study was to evaluate alterations in the timecourse of daily binge (drinking-in-the-dark; DID) ethanol consumption. We gave 14 daily 2 hour DID ethanol or water access sessions to male C57BL/6J (B6) mice using a state of the art volumetric drinking monitoring device. We then, primarily as a proof-of-principle, used the GABAB allosteric modulator GS39783 (GS) to determine how this compound influenced the timecourse of binge-like ethanol intake. The rate of ethanol consumption increased dramatically over sessions with the majority occurring in the first few minutes of the final session. Additionally, ethanol consumption occurring immediately following access was almost completely abolished in mice pre-treated with GS; an effect which was ethanol-specific only at this early time interval. These data characterize progressive alterations in the rate of ethanol intake using the DID model and suggest that careful consideration of prior ethanol history and timing of drug administration are warranted when interpreting results of pre-clinical drug administration studies.
authors.forename: David N
authors.initials: DN
authors.lastname: Linsenbardt
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Boehm
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D063425:Binge Drinking / Q000503:physiopathology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology; D003624:Darkness; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D006702:Homing Behavior / Q000187:drug effects; D007267:Injections; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D002492:Central Nervous System Depressants; D003517:Cyclopentanes; D018757:GABA Modulators; C478058:N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine; D011743:Pyrimidines; D000431:Ethanol