Sensibilização comportamental ao etanol em camundongos: avaliação da expressão da proteína (delta)FosB e possíveis efeitos da lateralização na via mesocorticolímbica

Abstract

One of the main challenges of ethanol addiction research is to unveil the brain changes responsible for the transition from recreational drug use to addiction. In this context, behavioral sensitization has been used as a model of neuroplasticity induced by repeated administration of abuse drugs. ΔFosB is a transcription factor that accumulates in the brain after chronic drug exposure and constitutes one of the most important neuroplastic alteration induced by repeated drug use. Recent data have suggested a distinct role of brain hemispheres in modulation of emotions. However, there are no studies about brain lateralization and ethanol-induced behavioral alterations or neuroplasticity. Thus, we evaluated the expression of ΔFosB in brain areas related to alcohol effect comparing the right and left brain hemispheres. For this, Swiss mice were submitted to behavioral sensitization procedure with ethanol or vehicle repeated i.p. administrations. According to their increase on ethanol-induced locomotor activity they were separated in EtOH-Sensitized and EtOH-Not Sensitized or Vehicle treated. Later, mice had their brain processed for ΔFosB immunohistochemistry. We observed that EtOH-Sensitized group has increased ΔFosB expression in in both hemispheres of dorsal medial striatum and infralimbic cortex. In the orbitofrontal cortex and nucleus accumbens shell, the increase of ΔFosB occurred only in the left hemisphere. In contrast, EtOH-Not Sensitized group demonstrated an elevated ΔFosB expression in both hemispheres in granular/disgranular insular cortex but only in right hemisphere of orbitofrontal cortex, cingulate cortex and ventral tegmental area. In central amygdala all groups treated with ethanol had increased ΔFosB expression only in right hemisphere. Our results point predominance of neuroplasticity in the left hemisphere of ethanol behaviorally sensitized animals while neuroplasticity in the right hemisphere seems to protect from ethanol behavioral alterations.