Efeitos da cafeína na manifestação dos déficits neurocomportamentais decorrentes da exposição ao etanol durante o desenvolvimento

Abstract

Ethanol and caffeine are two of the most consumed neuroactive drugs in the world. While caffeine consumption is considered safe, ethanol consumption during pregnancy is responsible for a number of neurobehavioral disorders in children and adolescents. In spite of the epidemiological evidence of the combined use of caffeine and ethanol by pregnant women, the interactions between these two drugs have received little attention in experimental studies. In the current study, we analyzed the effects of co-exposure to caffeine and ethanol during development on the anxiety-like behavior, learning and memory, rotational behavior and cortical levels of oxidative stress of mice. In this sense, Swiss mice were exposed from the first gestational day to the 21st postnatal (PN21) day to one of three solutions: 1) a solution containing caffeine 0.1 g/l (group CAF1); 2) a solution containing caffeine 0.3g/l (group CAF3); 3) filtered tap water (group CAF0). Every other day, from PN2 to PN8, animals in each litter were i.p injected with one of the following solutions: 1) 0.25 µl/g ethanol (group ETOH25); 2) 0.5 µl/g ethanol (group ETOH50); 3) saline solution (group ETOH0). The behavioral tests were performed between PN30 and PN35. The anxiety-like behavior was evaluated in the locomotor activity was analyzed in the elevated plus maze test (EPM). The passive avoidance test was used to assess learning and memory. The rotational behavior was assessed in the free-swimming test. On PN9 and PN30, the oxidative stress was evaluated by the measurements of thiobarbuturic acid reactive species (TBARS), antioxidant capacity (DPPH) and protein carbonylation. In EPM, animals from the ETOH50 group were less anxious than those from the ETOH25 and SALINE groups. In passive avoidance, a learning and memory impairment were observed only in males exposed to ethanol. In the free-swimming test, mice exposed to the higher dose of caffeine had fewer angular displacements and mice exposed to the higher dose of ethanol had a greater number of angular displacements. Of note, the effects of ethanol were less evident in the group animals exposed to higher caffeine dose in all behavioral tests. Regarding oxidative stress assays, while the exposure to caffeine had an antioxidant effect and exposure to ethanol was not able to affect oxidative stress levels. Our data corroborate studies that show that early exposure to ethanol promotes a number of neurobehavioral disorders. In addition, gestational exposure to caffeine may play a protective role in the manifestation of neurobehavioral deficits caused by early exposure to ethanol.