Os efeitos locomotores e exploratórios da infusão contínua de nicotina em camundongos Suíços adolescentes são modulados de forma sexo- e idade-dependente pela exposição ao Ambiente Enriquecido na infância

Abstract

Environmental enrichment (EE) consists of an experimental model in which animals are exposed to an environment that provides a variety of cognitive, sensory and motor stimuli. Research in mice has shown that the EE can stimulate neurogenesis, for example in the hippocampus, throughout life. These structural changes result in improved cognitive function, which is observed, for example, through improvements in tasks involving memory and learning. The EE also has behavioral benefits regarding the modulation of mood and social contact. EE exposure during development can have an impact on the neurophysiological responses to drugs of abuse due to its action on the reward system of the brain. Studies have suggested that EE is a new possibility of neurocomportamental approach to changes in the function of the central nervous system, particularly in relation to its role both in prevention and in the reversal of the effects of addiction to various drugs of abuse. In fact, the EE has been assigned a protective role regarding the development of this dependency. Here, our goal was to evaluate, in adolescent (postnatal day - PN - 45) and adult (PN75) Swiss mice, the impact of prior exposure to the enriched environment during childhood on the effects derived from treatment with nicotine during adolescence on the following behavioral parameters: locomotor activity, search for new stimuli and anxiety. Also studied were the contents of dopamine, DOPAC and norepinephrine. From PN15 to PN30 (childhood), experimental litters were separated into two groups: those exposed to the EE and those exposed to the control environment (CONT). From PN30 to PN45 (adolescence), animals were either treated with nicotine (NIC; osmotic minipumps s.c.) or saline (SAL). Four experimental groups were thus used: CONT-SAL, CONT-NIC, EE-SAL and EE-NIC. The animals were evaluated, at PN45 (adolescence) or at PN75 (adulthood), initially in the open field (CA) and, 2 hours later, in the hole board arena (CV). In the CA, EE exposure increased locomotor activity of adolescent females. At adulthood, males treated with nicotine also showed an increase in locomotor activity. In the CV, EE exposure reversed the effects of nicotine on the number of explored holes both in adult females and males. EE exposure reduced the concentration of dopamine in the cortex of adult males, while the content of DOPAC was reduced in adult males exposed to EE and treated with nicotine. Besides, EE exposure increased the concentration of cortical noradrenaline in both adult females and males. Our results indicate a clear influence of the enriched environment exposure on animal behavior, modulating or even reversing the effects of subsequent nicotine in a sex-dependent manner.