Heterogeneity of nicotine actions in the rat cerebellum: an in vivo electrophysiologic study.
Much controversy surrounds the actions of nicotine on mammalian central neurons, especially with respect to the question of presence of multiple nicotine receptors and with respect to similarities of responses to those induced by acetylcholine (ACh). To resolve some of these complexities, the authors determined the effects of pressure-ejected nicotine on identified neurons in the cerebellar cortex of Sprague-Dawley rats under urethane anesthesia. Purkinje cells and interneurons were identified by their anatomical localization, discharge characteristics and responses to electrical stimulation of superficial parallel fibers. Locally applied nicotine altered single-unit activity in a manner strictly dependent on cell type. Pressure-ejected nicotine inhibited Purkinje cells (50/51) and excited cerebellar interneurons (22/22). The effects of nicotine on cell discharge rate were probably receptor mediated because "classical" nondepolarizing nicotinic antagonists selectively blocked the agonistic actions of nicotine. A curare-sensitive site (neuromuscular type) was found to mediate the excitatory effects of nicotine, and a hexamethonium-sensitive site (ganglionic type) was found to mediate the inhibitory effects of nicotine. ACh mimicked the effects of nicotine on both cell classes although muscarinic interactions were also observed. The inhibitory effects of ACh on Purkinje cells were antagonized by the ganglionic blocker hexamethonium only if muscarinic receptors were simultaneously blocked via systemic administration of scopolamine. The excitatory effects of ACh on interneurons, on the other hand, were antagonized by the neuromuscular blocker curare even in the absence of a muscarinic antagonist. No interactions of curare and hexamethonium were observed with the amino acid transmitters gamma-aminobutyric acid (Purkinje cells) and glutamate (interneurons).
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D003472:Curare / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000145:classification / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D006584:Hexamethonium Compounds; D011978:Receptors, Nicotinic; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D003472:Curare; D000109:Acetylcholine