Nicotine-induced inhibition of cerebellar Purkinje neurons: specific actions of nicotine and selective blockade by mecamylamine.
The specificity and pharmacological characteristics of the effects of local administration of nicotine on cerebellar Purkinje cells in the rat were examined electrophysiologically. Local application of nicotine, whether by pressure-ejection or by iontophoresis, depressed the spontaneous discharge of Purkinje neurons in a reversible and dose-dependent manner. This action could not be mimicked by local application of vehicle alone. The inhibitory effects of (-)-nicotine were several-fold more potent than that of the (+)-enantiomer. Systemic administration of the ganglion blocker mecamylamine reliably and reproducibly antagonized the nicotine-induced inhibitions of Purkinje cells whereas nicotine-induced excitation of interneurons was not altered. Local pressure-ejection of mecamylamine also antagonized the inhibitory actions of nicotine, administered by iontophoresis. Since the central effects of nicotine on behavior are stereospecific and sensitive to mecamylamine, the data in this study further support the hypothesis that the actions of nicotine on Purkinje neurons are mediated by ganglionic-like receptors. These findings also suggest that the Purkinje cell may serve as a good cellular model for studies on central pharmacology of nicotine.
de la Garza
R
R
Veterans Administration Medical Center, Denver, Colorado 80262.
Freedman
R
R
Hoffer
J
J
D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D007478:Iontophoresis; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D008464:Mecamylamine; D009538:Nicotine