Consequences of low levels of nicotinic acetylcholine receptors in schizophrenia for drug development

Abstract

AbstractThe incidence of smoking in the mentally ill is much higher than in the general population and is inordinately high in schizophrenia. It has been suggested that this might be an attempt to self‐medicate an underlying biological deficit. The receptors that mediate nicotinic responses are decreased in many regions of postmortem brain in schizophrenic smokers, compared to control smokers. Patients exhibit differential responses to nicotine in a number of behavioral, cognitive, and metabolic measures. As nicotine regulates the release of a large number of neurotransmitters, it is likely that differences in down‐stream neuroadaptation of other transmitter/receptor systems would result from the reduced level of nicotinic receptors in these patients. The disparate responses to nicotine have consequences for the development of cholinergic drug therapies in schizophrenia. Drug Dev. Res. 60:127–136, 2003. © 2003 Wiley‐Liss, Inc.