Intracerebellar nicotinic-cholinergic participation in the cerebellar adenosinergic modulation of ethanol-induced motor incoordination in mice

Abstract

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 μg) and trimethaphan (100 ng), the purported nicotinic-cholinergic antagonists. Finally, the ICB injection of adenosine agonists, N 6-cyclohexyladenosine (CHA) or5′- 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.