Locomotor activity responses to ethanol, other alcohols, and GABA-A acting compounds in forward- and reverse-selected FAST and SLOW mouse lines.

Mice selectively bred for high (FAST) or low (SLOW) locomotor stimulant response to ethanol have been found to differ in response to drugs with gamma-aminobutyric acid (GABA)-ergic actions. Reverse selection produced lines that are similar in sensitivity to ethanol stimulation (r-FAST and r-SLOW) and provided a unique model for testing hypotheses about shared genetic influence on sensitivity to ethanol and GABAergic drugs. FAST mice were more stimulated than SLOW mice by all drugs tested: ethanol, methanol, n-propanol, t-butanol, pentobarbital, diazepam, and allopregnanolone. In contrast, r-FAST and r-SLOW mice differed in sensitivity to only a few isolated drug doses. Locomotor responses of each reverse-selected line were significantly different from the responses of their respective forward-selected line for all drugs. Results support an effect of selection for ethanol sensitivity on allosteric modulation of the GABA-A receptor.