Curso temporal dos efeitos da co-exposição a fumaça do cigarro e cafeína: efeitos sobre a reposta emocional em camundongos adolescentes

Abstract

Caffeine and tobacco smoke are among the most frequently selfadministered licit psychoactive drugs in the world. In addition, a number of epidemiologic studies have documented a positive correlation between caffeine consumption and tobacco smoke. However, little is known about the basic neurobiology of the combined exposure in the adolescent brain, age which usually begin the use of tobacco smoke. Here, we investigated the short- and long-term effects of long life exposure of cafeine and/or adolescent tobacco smoke on anxiety levels and depression-like behavior. Caffeine was administrated in a lifelong model (0.1 g/l to drink). From postnatal day 30-45, Swiss mice were exposed to tobacco smoke (SMK--whole body exposure, 8 h/day) generated from research cigarettes type 3R4F (nicotine = 0.73 mg/per cigarette). Four groups were analyzed: (1) CAF+SMK exposure; (2) SMK exposure; (3) CAF exposure; (4) Control. Anxiety levels were assessed with the elevated plus maze (EPM) and depressive-like behavior were assessed with the forced swimming test (FST). The behavioral analysis was assessed by the end of smoke exposure (PN45) as well as during adolescence (PN55) and long-term (PN75) withdrawal. In the present work, caffeine exposure generated reduction in the decision making time (time in center of maze) in EPM during adolescence (PN45 and PN55). The long-term withdrawal of tobacco smoke increase decision making time which was reversed by caffeine. In addition, the exposure of caffeine was able to elicit increase anxiety in animals with long-term tobacco smoke withdrawal. Caffeine exposure during tobacco withdrawal during adolescence induced a increase climbing behavior in FST. At adulthood, both long life exposure of caffeine and long-term tobacco exposure withdrawal induced reduction of immobility time in FST, an antidepressant effect which was mitigated by co-exposure. The present study provides experimental evidence that caffeine and tobacco smoke during adolescence interact resulting in emotional dysregulation during both exposure and smoke withdrawal. Particularly, anxiety levels do not seem to be relevant during a short-term SMK deprivation, however, increased anxiety during long-term tobacco withdrawal in CAF+SMK animals demonstrate late-emergent effects. In these sense, our data suggest that longlife caffeine exposure may be an important factor in maintaining tobacco smoking.