Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar γ-aminobutyric acid type A (GABA(A)) receptor α6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of α6- and nonα6-containing GABA(A) receptor subtypes. Motor performance in a tilting plane test was largely unaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1-10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and zg-63 (both at 40 mg/kg, IF), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IF) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IF) impaired performance of the ANT but not AT animals. These data, supported by results from blain regional autoradiography of [H]Ro15-4513 and membrane binding of [H]ZG-63 and [S]TBPS as influenced by these ligands, strongly suggest that only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) α6-containing GABA(A) receptors are able to produce motor impairment in the ANT rats.