Ethanol-induced locomotor sensitization: Neuronal activation in the nucleus accumbens and medial prefrontal cortex

•Ethanol-induced behavioral sensitization in mice.•Ethanol-induced behavioral sensitization is followed by an increase in Nucleus Accumbens Shell activation.•Acute and chronic ethanol administration increased Fos immunoreactive nuclei in cingulate and pre-limbic cortex subregions.•Repeated Ethanol administration decreased ARC protein levels in the Nucleus Accumbens and the Medial Prefrontal Cortex. Ethanol consumption may promote neuroplasticity and alterations in synapses, resulting in modifications in neuronal activity. Here, we treated male Swiss mice with ethanol (2.2 g/kg) or saline once per day for 21 consecutive days. Nine days after the last ethanol administration, they received a challenge injection of ethanol or saline, and we assessed locomotor activity. After the behavioral analysis, we evaluated neuronal activation in the medial Prefrontal Cortex (Cingulate, Prelimbic, and Infralimbic) and the Nucleus Accumbens (Shell and Core) using Fos/DAB immunohistochemistry. In another group of animals, we performed the quantitative analysis of the ARC and PSD-95 protein levels by Western blotting in the medial prefrontal cortex and nucleus accumbens brain areas. Repeated ethanol administration produced locomotor sensitization, accompanied by an increase in the nucleus accumbens shell's activation but not core. Furthermore, the ethanol pretreatment reduced ARC expression in the nucleus accumbens and medial prefrontal cortex. Our results suggest the participation of the nucleus accumbens shell in ethanol behavioral sensitization and add new pieces of evidence that neuroplasticity in synapses may contribute to the mechanism underlying this behavior.