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Are nicotinic receptors activated or inhibited following chronic nicotine treatment?
Author(s) -
Collins Allan C.,
Marks Michael J.
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199607/08)38:3/4<231::aid-ddr12>3.0.co;2-1
Subject(s) - nicotine , downregulation and upregulation , desensitization (medicine) , nicotinic agonist , receptor , pharmacology , acetylcholine receptor , drug tolerance , chemistry , endocrinology , medicine , biochemistry , gene
Chronic nicotine treatment generally results in altered response, generally tolerance, to many of the behavioral and physiological effects produced by nicotine. Chronic nicotine treatment also results in an increase, or upregulation, of brain nicotinic receptors (nAChRs), particularly those receptors that bind nicotine with high affinity (α4β2 subtypes). Initial studies suggested that this upregulation might be causally related to the development of tolerance, but more recent studies have shown that receptor upregulation varies markedly across brain regions and that upregulation does not covary with tolerance in all mouse strains, thereby dissociating receptor changes from tolerance development. More recent studies indicate that acute administration of nicotine activates nAChRs, but this is quickly followed by desensitization, and desensitization can be produced by concentrations of nicotine less than those required to activate the nAChRs. In addition, chronic nicotine treatment may inactivate brain nAChRs. While it is unknown whether the desensitization and inactivation processes vary among nAChR subtypes or among brain regions, it seems more reasonable to speculate that changes in nAChR function underlie tolerance to nicotine. Drug Dev. Res. 38:231–242 © 1996 Wiley‐Liss, Inc.