Desensitization of central cholinergic mechanisms and neuroadaptation to nicotine |
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Authors: | Enrique L M Ochoa Lan Li Mark G McNamee |
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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 |
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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. |
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Keywords: | Neuronal nicotinic receptors desensitization of pre- and postsynaptic cholinergic transmission nicotinic receptor upregulation dependence on nicotine neuroadaptation to nicotine |
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