Effects of GABA antagonists and habituation to novelty on ethanol-induced locomotor activity in mice.

The effects of the gamma-aminobutyric acid (GABA) antagonists picrotoxin and bicuculline on ethanol-induced motor excitation were assessed on habituated and non-habituated mice. Habituated mice were exposed to the testing apparatus for 30 min on 4 consecutive days before testing. Mice were treated with several doses of ethanol (0.8, 1.2 and 1.6 g/kg, intraperitoneally) and at each dose were pretreated with picrotoxin (0.25, 0.5 and 1.0 mg/kg, i.p.) or bicuculline (0.5, 1.0 and 2.0 mg/kg, i.p.). Habituated animals had consistently lower scores than non-habituated animals throughout the experiment. Ethanol alone produced a significant increase in motor activity. Picrotoxin and bicuculline alone decreased motor activity only at the two higher doses in both habituated and non-habituated mice. For the non-habituated mice, picrotoxin and bicuculline at the lowest doses decreased ethanol induced motor activity at the 0.8 and 1.2 g/kg ethanol doses, whereas in habituated mice, only bicuculline attenuated activity. At the highest dose of ethanol, picrotoxin increased ethanol-induced excitation for both non-habituated and habituated animals, whereas bicuculline only augmented the activity of the non-habituated animals at this ethanol dose. Neither antagonist affected blood-ethanol levels. These results suggest that habituation affects not only motor activity per se but also changes in activity due to the combination of GABA antagonists and ethanol.