Combined exposure to tobacco smoke and ethanol during adolescence leads to short- and long-term modulation of anxiety-like behavior.

Abstract

Tobacco smoking is associated with alcohol drinking and consumption of both drugs typically begins during adolescence. Since anxiety is considered a relevant factor for both smoking and drinking due to its motivating force for a continued consumption, anxiety alterations shared by these two drugs could explain their co-use and co-abuse. Here, we investigated the short- and long-term effects of adolescent tobacco smoke and/or ethanol exposure on anxiety levels. From postnatal day 30-45, Swiss mice were exposed to tobacco smoke (SMK--whole body exposure, 8 h/day) and/or ethanol (ETOH--25% solution, 2g/kg i.p. injected every other day) as follows: (1) SMK+ETOH exposure; (2) SMK exposure; (3) ETOH exposure; (4) Control. Anxiety levels were assessed with the elevated plus maze and open field tests. By the end of exposure, SMK female mice presented an anxiolytic response in the elevated plus maze and this response was intensified by co-exposure to ethanol. A short-term deprivation from SMK elicited an anxiogenic state in females in this maze. Although neither smoke nor ethanol effects persisted one month post-exposure, SMK+ETOH male and female mice exhibited an anxiogenic response in the open field. Adolescent female mice are more susceptible to the anxiolytic effects of SMK. The stronger effect in SMK+ETOH group suggests that, in females, the combined exposure leads to lower anxiety levels. Anxiety levels do not seem to be relevant during a short-term SMK+ETOH deprivation, however, increased anxiety during long-term smoking and drinking deprivation demonstrate late-emergent effects both in males and females.