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Selective antagonism of nicotine actions in the rat cerebellum with alpha-bungarotoxin
R de la Garza1, T J McGuire, R Freedman
1University of Colorado Health Sciences Center, Department of Pharmacology, Denver 80262.
Abstract:
Nicotine, locally applied to identified neurons in the rat cerebellar cortex, excites inhibitory interneurons, but depresses the discharge of Purkinje cells. Alpha-bungarotoxin blocked the excitatory actions of nicotine on the inhibitory interneurons. The antagonism of nicotine excitatory actions is largely irreversible and also insurmountable with higher doses of nicotine. The antagonism by alpha-bungarotoxin is, in addition, selective since there is no blockade of the inhibitory actions of nicotine on Purkinje neurons. The present data suggest that the excitatory actions of nicotine on inhibitory interneurons are mediated by neuromuscular-type nicotinic receptors in the cerebellum. Moreover, the present data also supports the hypothesis of multiple nicotinic sites of action in mammalian brain.