Modification of the actions of ethanol by centrally active peptides.
Ethanol (2.0-5.0 g/kg, IP) caused a dose-related impairment of the aerial righting reflex of mice 60 min after injection. Ethanol (3.5 g/kg, IP) given simultaneously with neurotensin (30 micrograms, IC), bombesin (30 micrograms, IC) or beta-endorphin (20 micrograms, IC) caused a greater impairment of the reflex than ethanol alone. Simultaneous treatment with ethanol (4.0 g/kg, IP) and thyrotropin-releasing hormone (TRH, 3.0-30 micrograms, IC) caused less impairment of this measure than ethanol alone. None of the peptides altered the height of aerial righting when administered alone, or when administered with ethanol no peptide altered blood or brain ethanol content. Unexpectedly, TRH (20 and 40 mg/kg, IP) potentiated the action of ethanol by increasing punished licking in water-deprived rats, rather than antagonizing this acute action of ethanol. Like ethanol (1.0 and 2.0 g/kg, IP), beta-endorphin (100 micrograms, IC) suppressed ethanol-withdrawal tremor and audiogenic-seizure susceptibility in ethanol-dependent rats. beta-Endorphin (1 microgram) and bombesin (10 and 30 micrograms, IC) reduced only audiogenic-seizure susceptibility. TRH (10-100 micrograms, IC, or 1-40 mg/kg, IV) and neurotensin (10-100 micrograms, IC) had no effect on these ethanol-withdrawal signs. These findings suggest that centrally active peptides may play a role in certain acute and chronic actions of ethanol. Because TRH, neurotensin, bombesin and beta-endorphin do not alter all actions of ethanol in the same way, an interaction of ethanol with many functionally independent neuronal circuits is suggested.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001839:Bombesin / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009496:Neurotensin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D001615:beta-Endorphin
D004723:Endorphins; D010455:Peptides; D009496:Neurotensin; D000431:Ethanol; D013973:Thyrotropin-Releasing Hormone; D001615:beta-Endorphin; D001839:Bombesin