Potential regulation of nicotine and ethanol actions by alpha 4-containingnicotinic receptors

A restriction fragment length polymorphism (RFLP) associated with a major n icotinic receptor subunit (i.e., alpha4) has been identified in two mouse l ines that were selectively bred for differences in sensitivity to ethanol. These mice, referred to as Long-Sleep (LS) and Short-Sleep (SS) mice, also differ in sensitivity to several effects of nicotine. The potential role of the alpha4 RFLP in regulating several responses to nicotine and ethanol wa s evaluated by using the LSxSS-derived recombinant inbred (RI) strains. Tho se RI strains that carried the LS-like a4 RFLP were more sensitive to the d epressant effects of nicotine on Y-maze crossing and rearing activities and ethanol-induced increases in Y-maze crossing activity than were those RI s trains that carry the SS-like a4 RFLP. The LS-like RI strains were also mor e sensitive to nicotine-induced hypothermia. The RFLP was not associated wi th strain differences in ethanol-induced body temperature or sleep time. Th e potential role of the RFLP in regulating ethanol and nicotine consumption was evaluated in heterogeneous stock (HS) mice. An association was found b etween the alpha4 RFLP and variation in ethanol consumption, but not in nic otine consumption, as measured in a four-bottle choice test. Recent studies of ethanol and tobacco abuse by human beings suggest that common genes may influence these two forms of substance abuse. The results of the studies r eported here suggest that the alpha4 nicotinic receptor gene should be eval uated for its potential role in regulating ethanol and tobacco abuse in hum an beings. (C) 2001 Elsevier Science Inc. All rights reserved.