Propofol-induced ataxia and hypnosis in rat lines selected for differential alcohol sensitivity

An alcohol-sensitive rat line, selectively bred for high sensitivity to ethanol-induced motor impairment, also exhibits greater sensitivity to gamma-aminobutyric acid type A (GABA(A)) receptor agonists, such as benzodiazepines and barbiturates, than an alcohol-insensitive rat line. We have investigated whether this difference was also maintained for the most recent intravenous anaesthetic, propofol. Propofol (100 mg/kg, intraperitoneally)induced similar sleep times and produced identical plasma propofol concentrations in alcohol-sensitive and alcohol-insensitive rat lines. At lower doses (50 and 75, but not 25 mg/kg), propofol produced a greater motor impairment in a tilting plane test in alcohol-sensitive than alcohol-insensitive rats shortly after the injection. Binding of a convulsant, [S-35]t-butylbicyclophosphorothionate, to cerebellar and cerebrocortical GABA(A) receptors in the presence of 2 mu M GABA was similarly affected by low micromolar propofol concentrations in both rat lines, while in the absence of GABA, propofol was slightly less potent in the alcohol-sensitive than alcohol-insensitive line. These data indicate that alcohol-sensitive rats show transiently enhanced sensitivity to an ataxic, but not to a hypnotic dose of propofol, which cannot be explained by sensitivity differences to propofol in GABAA receptors determined in a binding assay using brain membrane homogenates.