ARE NICOTINIC RECEPTORS ACTIVATED OR INHIBITED FOLLOWING CHRONIC NICOTINE TREATMENT

Chronic nicotine treatment generally results in altered response, gene rally tolerance, to many of the behavioral and physiological effects p roduced by nicotine. Chronic nicotine treatment also results in an inc rease, or upregulation, of brain nicotinic receptors (nAChRs), particu larly those receptors that bind nicotine with high affinity (alpha 4 b eta 2 subtypes). Initial studies suggested that this upregulation migh t 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 toleranc e development. More recent studies indicate that acute administration of nicotine activates nAChRs, but this is quickly followed by desensit ization, and desensitization can be produced by concentrations of nico tine less than those required to activate the nAChRs. In addition, chr onic nicotine treatment may inactivate brain nAChRs. While it is unkno wn whether the desensitization and inactivation processes vary among n AChR subtypes or among brain regions, it seems more reasonable to spec ulate that changes in nAChR function underlie tolerance to nicotine. ( C) 1996 Wiley-Liss, Inc.