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.
Koechling
U M
UM
Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
Smith
B R
BR
Amit
Z
Z
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D018756:GABA Antagonists; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D012931:Social Environment
D001640:Bicuculline; D000431:Ethanol; D018756:GABA Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A