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Camarini R, Rueda AV, Rae MB, Amaral BH, Taveiros-Silva NKG, Contó MB.

Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil
We have investigated the influence of positive environmental interventions (environmental enrichment or voluntary exercise) on both the rewarding effects of alcohol and alcohol sensitization. Environmental enrichment (EE) consists of a combination of motor, sensory, social and cognitive stimuli. In the experiments with voluntary exercise, 4 running wheels were placed in their home cage.
We have demonstrated that expression of ethanol-induced behavioral sensitization can be prevented by a 7-day exposure to EE.
The effects of a short EE on several behavioral parameters, corticosterone levels and BDNF levels were investigated. No changes on anxiety, anhedonia and depression behaviors were found. In the open-field, EE mice showed an initial peak of locomotion followed by a sharp decline, while the controls exhibited a constant locomotor activity. When exposed to a stressful situation, corticosterone levels were blunted in EE mice, as compared to controls. We tested the effects of EE on ethanol-induced corticosterone levels and no changes were found. Our data suggest that EE modulates the HPA axis, by changing the corticosterone response following acute stress but not after ethanol exposure.
As BDNF may play a role in ethanol sensitization, and its levels are decreased in the frontal cortex of mice exposed to EE, we investigated if the reversal in ethanol sensitization by EE was followed by changes in the expression of selected miRNAs that interact with the BDNF mRNA 3’UTR. No significant differences in the expression of microRNAs (miR-9, miR-124a, miR-132, miR-153 or let-7d) were found. Although EE consistently prevented ethanol sensitization, it increased CPP to ethanol. On the other hand, mice exposed to voluntary exercise did not develop CPP to ethanol. Voluntary exercise also prevented ethanol-induced CREB expression in the nucleus accumbens. A positive correlation between CPP score and CREB expression was found in controls, but not in the voluntary exercise group. This result suggests that a cellular response associated with ethanol CPP was prevented by voluntary exercise. Financial Support: FAPESP (15/02397-0).