RT Journal Article SR Electronic T1 Role of the gamma-aminobutyric acid receptor/chloride channel complex in tolerance to ethanol and cross-tolerance to diazepam and pentobarbital. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 108 OP 113 VO 261 IS 1 A1 S J Mihic A1 H Kalant A1 J F Liu A1 P H Wu YR 1992 UL http://jpet.aspetjournals.org/content/261/1/108.abstract AB The role of the gamma-aminobutyric acid (GABA) receptor/chloride channel complex in the development of tolerance to ethanol and cross-tolerance to diazepam and pentobarbital was assessed. Rats given a low (1.8 g/kg) dose of ethanol before daily practice on the moving belt test of motor incoordination, and those given a high daily dose (3.6 g/kg) not paired with practice, showed tolerance to ethanol and cross-tolerance to diazepam and pentobarbital, whereas rats receiving 1.8 g/kg of ethanol after practice did not. Control rats were trained on the moving belt, but received no ethanol treatment. No differences were seen among the treatment groups in the abilities of GABA or ethanol to increase 36Cl uptake into cerebral cortical microsacs. However, diazepam potentiation of GABA-mediated chloride flux was significantly lower in rats receiving daily intoxicated practice, but only if they received an i.p. injection of ethanol 1 hr before sacrifice. The degree of pentobarbital potentiation of the effect of GABA did not correlate with the behavioral cross-tolerance observed. The results indicate that behaviorally augmented cross-tolerance from ethanol to diazepam correlates incompletely with changes on the biochemical level.