INTRACEREBELLAR NICOTINIC-CHOLINERGIC PARTICIPATION IN THE CEREBELLARADENOSINERGIC 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 psycho active drugs. Recently, we reported behavioral interactions between (- )-nicotine, (-)-cotinine and ethanol within the CNS. The present repor t is a confirmation and an extension of that study. Using a 2 g/kg eth anol-induced motor incoordination (EIMI) as the test response, possibl e behavioral interactions between (-)-nicotine, (-)-cotinine and ethan ol and between (-)-nicotine, (-)-cotinine and adenosine agonist + etha nol in the cerebellum were investigated. (-)-Nicotine, 0.625, 1.25 and 5 ng intracerebrally (ICB) significantly attenuated EIMI in a dose-re lated manner. Likewise, ICB injection of 1.25, 2.5, and 5 ng (-)-cotin ine, a major metabolite of nicotine, significantly attenuated EIMI aft er the same i.p. dose of ethanol as in case of(-)-nicotine but less ma rkedly compared to (-)-nicotine. No change in normal motor coordinatio n was observed when the highest dose of (-)-nicotine or (-)-cotinine w as 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 mu g) and trimethaphan (100 ng), the purported nicotinic-cholinergic anta gonists. Finally, the ICB injection of adenosine agonists, N-6-cyclohe xyladenosine (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 c holinergic interaction and modulation of EIMI. The data also suggested participation of cerebellar nicotinic-cholinergic receptors in EIMI.