Efeitos da exposição de camundongos adolescentes à fumaça de cigarros contendo diferentes níveis de nicotina: alterações bioquímicas e comportamentais

Abstract

Tobacco consumption is one of the most important public health challenges. Despite that, there is a lack of experimental studies that investigate the effects of tobacco smoke exposure during adolescence. The current study was undertaken to investigate the effects of tobacco smoke generated from cigarretes containing either high or low levels of nicotine in the behavior and cholinergic system of mice exposed during adolescence. From postnatal day (PN) 30 to 45, Swiss mice of both sexes were exposed to tobacco smoke (whole body exposure for 8 hr/day and 7 days/week) generated from one of two reference research cigarettes: type 2R1F (HighNIC group - nicotine = 1.74 mg/cigarette) or type 4A1 (LowNIC group - nicotine = 0.14 mg/cigarette). Control mice (CT) were exposed to current air. At the end of the exposure period (PN45) we assessed the levels of cotinine (nicotine metabolite) in serum of a separate group of mice. By the end of exposure (PN44-45), during short-term (PN49-50) and long-term withdrawal (PN74-75), mice were submitted to the elevated plus maze and hole board tests. There were no differences in anxiety among groups in the maze. In the hole board, the effects were largely dependent on the type of cigarette. By the end of the exposure period, HighNic animals explored a larger number of holes and LowNic mice explored fewer holes when compared to CT animals. During a short-term withdrawal, LowNic mice still explored fewer holes while, during long-term withdrawal, there was a late-emergent increase in exploration in HighNic females. Regarding the cholinergic system, we assessed nicotinic acetylcholine receptor (nAChR) binding, [(3)H]hemicholinium-3 (HC-3) binding to the high-affinity choline transporter, choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activities in the cerebral cortex of mice decapitated after the last behavioral test. Both Low and HighNic mice presented nAChR upregulation during exposure, however, this effect failed to persist at withdrawal. Effects on HC-3 binding and ChAT were sex-dependent. Regarding HC-3, effects were identified during withdrawal: In the short-term, while male mice from both Low and HighNic groups presented increased binding, it was decreased in females. Distinctively, in the long-term, a late-emergent decrease was identified in LowNic males and an increase was evident in HighNic females. ChAT activity was decreased in Low and HighNic males by the end of exposure. The decrease was followed by late-emergent increased activity in HighNic males during a short-term withdrawal. AChE activity was not affected by tobacco smoke exposure and withdrawal. These results indicate that exposure to cigarette smoke affects novelty seeking behavior and alters biomarkers of cholinergic function. The pattern of changes depends on the type of cigarette.