Intracerebellar nicotinic-cholinergic participation in the cerebellar adenosinergic modulation of ethanol-induced motor incoordination in mice.
Many epidemiological studies have suggested a high correlation between the use of tobacco and ethanol, the two most frequently abused psychoactive drugs. Recently, we reported behavioral interactions between (-)-nicotine, (-)-cotinine and ethanol within the CNS. The present report is a confirmation and an extension of that study. Using a 2 g/kg ethanol-induced motor incoordination (EIMI) as the test response, possible behavioral interactions between (-)-nicotine, (-)-cotinine and ethanol and between (-)-nicotine, (-)-cotinine and adenosine agonist + ethanol in the cerebellum were investigated. (-)-Nicotine, 0.625, 1.25 and 5 ng intracerebellarly (ICB) significantly attenuated EIMI in a dose-related manner. Likewise, ICB injection of 1.25, 2.5, and 5 ng (-)-cotinine, a major metabolite of nicotine, significantly attenuated EIMI after the same i.p. dose of ethanol as in case of (-)-nicotine but less markedly compared to (-)-nicotine. No change in normal motor coordination was observed when the highest dose of (-)-nicotine or (-)-cotinine was injected ICB followed by saline control, suggesting selectivity of their behavioral interactions with ethanol. The attenuation of EIMI by (-)-nicotine and (-)-cotinine was blocked by ICB hexamethonium (1 microgram) and trimethaphan (100 ng), the purported nicotinic-cholinergic antagonists. Finally, the ICB injection of adenosine agonists, N6-cyclohexyladenosine (CHA) or 5'-N-ethylcarboxamidoadenosine (NECA), produced marked accentuation of EIMI which was significantly antagonized by ICB (-)-nicotine and (-)-cotinine. The data obtained in the present study suggested, for the first time, a cerebellar adenosinergic-nicotinic cholinergic interaction and modulation of EIMI. The data also suggested participation of cerebellar nicotinic-cholinergic receptors in EIMI.
Dar
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MS
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.
Bowman
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ER
Li
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D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D003367:Cotinine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009068:Movement / Q000187:drug effects*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D013237:Stereoisomerism; D014294:Trimethaphan / Q000494:pharmacology
D006584:Hexamethonium Compounds; D018738:Hexamethonium; D000431:Ethanol; D014294:Trimethaphan; D009538:Nicotine; D003367:Cotinine; D000241:Adenosine