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Desensitization of central cholinergic mechanisms and neuroadaptation to nicotine
Authors:Enrique L M Ochoa  Lan Li  Mark G McNamee
Institution:(1) Division of Neonatology, Department of Pediatrics, School of Medicine, University of California at Davis, 95616 Davis, CA;(2) Department of Biochemistry and Biophysics, University of California at Davis, 95616 Davis, CA
Abstract:This review focuses on neuroadaptation to nicotine. The first part of the paper delineates some possible general mechanisms subserving neuroadaptation to commonly abused drugs. The postulated role of the mesocorticolimbic neuroanatomical pathway and drug-receptor desensitization mechanisms in the establishment of tolerance to, dependence on, and withdrawal from psychoactive drugs are discussed. The second part of the review deals with the pharmacological effects of nicotine at both pre- and postsynaptic locations within the central nervous system, and the still-perplexing upregulation of brain nicotine-binding sites seen after chronic nicotine administration. A special emphasis has been put on desensitization of presynaptic cholinergic mechanisms, and postsynaptic neuronal nicotinic-receptor function and its modulation by endogenous substances. A comparison with the inactivation process occuring at peripheral nicotinic receptors is also included. Finally, a hypothesis on the possible connections between desensitization of central cholinergic mechanisms and neuroadaptation to nicotine is advanced. A brief comment on the necessity of fully understanding the effects of nicotine on the developing nervous system closes this work.
Keywords:Neuronal nicotinic receptors  desensitization of pre- and postsynaptic cholinergic transmission  nicotinic receptor upregulation  dependence on nicotine  neuroadaptation to nicotine
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