Curso temporal dos efeitos da exposição à fumaça de cigarro e/ou etanol durante a adolescência no sistema serotoninérgico cerebral em camundongos suíços

Abstract

The use of tobacco and / or ethanol is associated with mood changes, especially when this use occurs during adolescence. These alterations may be involved in the etiology of abuse and dependence that makes adolescence a period of vulnerability to these drugs. Considering the participation of the serotonergic systems in the physiological mechanisms that modulate emotional states, the objectives of this study were to evaluate the changes promoted by cigarette smoke and / or ethanol exposure in the cerebral serotonergic system of adolescent mice. For this, Swiss adolescent mice were exposed to cigarette smoke and / or ethanol from the 30th to the 45 th postnatal day (PN), as follows: SMK + ETOH (exposure to cigarette smoke and i.p. ethanol); SMK (exposure to cigarette smoke and i.p. saline); ETOH (exposure to air and i.p. ethanol); (VEH (exposure to air and saline i.p.). The serotonergic system was evaluated in the cerebral cortex and hippocampus at the end of the period of exposure (PN45), during a short-term (PN50) and long-term (PN75) withdrawal. The following biomarkers were used for radioligand labeling: [³H] 8-OH-DPAT, which selectively binds to the serotonergic 5HT1A receptor; [³H] Ketanserin, which selectively binds to the 5HT2 receptor; and [³H] Paroxetine, which selectively binds to the 5HTT serotonergic transporter. In general, serotonergic markers were more affected during withdrawal . On PN45, only the hippocampus of males showed alterations in 5HTT binding:SMK animals showed increased binding and ETOH animals presented reduction. In this case, co-exposure nullified these effects. During the short-term withdrawal , female SMK animals were more susceptible than males, presenting reduction in the 5HT1A marking in the cerebral cortex and 5HTT in the cerebral cortex and hippocampus. Animals exposed to ethanol also showed a reduction in 5HT1A binding in both sexes in the hippocampus and only in males in the cerebral cortex. ETOH animals showed reduction of 5HTT binding in both sexes in the cerebral cortex and only in females in the hippocampus. In the co-exposed animals, there was a consistent reduction of 5HT1A and 5HTT. After a long period of cigarette smoke withdrawal , an increase in the labeling of 5HT1A and 5HT2 in the cerebral cortex was observed. Co-exposure to ethanol reversed this effect on 5HT1A. The present work provides experimental evidence that cigarette smoke and ethanol modify the serotonergic function during adolescence and interact with each other resulting in different alterations during exposure and withdrawal .