Influência do momento da exposição e do tamanho da ninhada na manifestação da hiperatividade locomotora de camundongos expostos ao etanol durante o desenvolvimento

Abstract

The consumption of ethanol during pregnancy leads to a series of long-lasting neurobehavioral disorders in the offspring, such as attention deficit hyperactivity disorder (ADHD). Studies in rodents have shown that the first 14 days of postnatal life, that encompass the brain growth spurt, is critical for the manifestation of locomotor hyperactivity. In this study, we investigated the influence of two factors with the potential to interfere in locomotive hyperactivity induced by ethanol during the brain growth spurt: the size of the litters and the moment of exposure. Each factor was investigated in an independent study. In the first study, Swiss mice from litters with less than eight or more than 12 pups received intraperitoneal (ip) ethanol (ETOH group, 5 g/kg) or saline solution (NaCl 0.9%, SAL group) injections on alternate days from the second postnatal day (PN2; PN1 = day of birth) to PN8. In the second study, 5 g / kg ip of ethanol or saline solution were injected during the brain growth spurt at the beginning (PN2), the middle (PN8), the end (PN14) and at all three moments (PN2, PN8 and PN14). Animals that were not injected (NORMAL group) were inserted in both studies. The locomotor activity was evaluated in PN25 (study 1) or PN30 (study 2) in the open field test. In addition, we evaluated the number of dopaminergic neurons in VTA in the second study. In the first study, litters with more than 12 pups from the ETOH group had a higher mortality rate than the animals from the SAL and NORMAL groups. In litters with less than 8 offspring, the mortality rate did not differ between groups. Regarding body mass, the animals from the litters with less than 8 pups of the ETOH group presented a lower mass gain than the NORMAL group. In the open field test, the locomotor activity of the animals did not vary according to the size of the litters, but the animals of the ETOH group had an increase of the activity in relation to the other groups. In the second study, the mortality rate of the group that received ethanol at the three ages was higher than that other groups. There were no differences in body mass gain during the exposure period, but mice that received ethanol at the three ages were lighter than those of the other groups in PN25. Regarding locomotor activity, no differences were observed between mice from NORMAL, SALINA and ETOH groups that received the injections in only one of the ages. In contrast, the locomotor activity of the ETOH group injected in the three ages was higher than that the other groups. Analysis of dopaminergic neurons did not reveal differences between groups. Our data suggest that, at least for locomotor activity, litter size does not affect the outcomes of ethanol exposure during the brain growth spurt. In contrast, locomotor hyperactivity induced by ethanol exposure during the period of brain growth spurt may depend on the frequency of exposure.