A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice.

The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.

Tobacco smoke containing high or low levels of nicotine during adolescence: effects on novelty-seeking and anxiety-like behaviors in mice.

RATIONALE: Thousands of adolescents start smoking daily but information on the effects of tobacco exposure on this age group is scarce. Moreover, the available animal models rely on the effects of nicotine, neglecting other neuroactive components of tobacco. OBJECTIVES: We investigated the effects of exposure of adolescent mice to tobacco smoke generated from cigarettes containing either high or low levels of nicotine on novelty seeking and anxiety-like behaviors. METHODS: From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8 h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74 mg nicotine/cigarette) or 4A1 (LowNic group: 0.14 mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. By the end (PN44-45), shortly (PN49-50), or long after (PN74-75) exposure, mice were tested on the elevated plus maze and on the hole board. RESULTS: While HighNic mice presented an increased number of head-dips (increased novelty-seeking) and decreased grooming (increased anxiety-like behavior) by the end of adolescent exposure, only the latter effect persisted shortly after its end. Distinctively, LowNic mice presented reduced head-dips both by the end and shortly after exposure as well as decreased grooming shortly and long after the end of exposure. Interestingly, only HighNic mice presented detectable cotinine (nicotine metabolite) serum levels (109.1 ± 24.0 ng/ml). CONCLUSION: Our results demonstrate that even adolescent exposure to tobacco smoke with very low nicotine content can have significant short- and long-term behavioral effects, supporting the hypothesis that adolescents can be particularly vulnerable to the effects of cigarette consumption.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.