Estudo dos efeitos da exposição ao etanol durante o desenvolvimento sobre o comportamento social em camundongos: comportamento agressivo e as alterações serotoninérgicas cerebrais

Abstract

Evidence that developmental ethanol exposure is associated with deficient social behavior, such as aggressive behavior, and that ethanol consumption is associated with violent crimes raises the possibility that individuals with fetal alcohol spectrum disorder show a worsened social deficit in response to ethanol exposure during adolescence. Here, male and female Swiss mice exposed to ethanol (Etoh, 5 g/Kg i.p., alternate days) during the brain growth spurt [postnatal day (P) 2 to 8] were used to assess social interaction and aggressive behavior parameters after an acute re-exposure to ethanol during adolescence. At P39, animals were administered with a single low ethanol dose (1 g/Kg) or water by gavage and were then evaluated in the three-chamber sociability test. Aggressive behavior was assessed by resident-intruder paradigm in males while social dominance was investigated by tube dominance test in both sexes. Testis structure and testosterone levels were evaluated in male mice. We also evaluated corticosterone serum levels and the frontal cerebral cortex serotoninergic system: Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations and 5HT2 receptors and 5HT transporter binding. Etoh males showed reductions in sociability. In addition, Etoh mice responded distinctively to acute low ethanol re-exposure during adolescence. Ethanol challenging reverted the alterations in social behavior, reduced corticosterone levels and increased 5-HT2 receptor binding in the cerebral cortex of male Etoh mice. No alterations were observed in 5-HT and 5-HIAA content. Early ethanol exposure increased the gonadosomatic index and the number of Leydig cells. In contrast, the thickness of seminiferous tube was decreased. No difference in testosterone levels was found. Regarding aggressive behavior, differences between groups were found only when the resident was challenged with a low ethanol dose (1g/Kg) before confrontation. ETOH resident mice showed increased number and spent more time in aggressive events. Female ETOH mice won more confrontations in the tube test. These data support the idea that ethanol exposure during the brain growth spurt impact social abilities during adolescent, alter ethanol re-exposure effects and suggest that stress response and the serotoninergic system play roles in this phenomenon. In addition, while basal aggressive levels were not affected, early ethanol exposure programs for increased susceptibility to ethanol-induced aggression in adolescent male mice.