PRECLINICAL STUDY: BRIEF REPORT: Epigenetic modulation at the CCR2 gene correlates with the maintenance of behavioral sensitization to methamphetamine

The intermittent administration of methamphetamine produces behavioral sensitization to methamphetamine. In the limbic forebrain, mainly including the nucleus accumbens, of mice that had been intermittently treated with methamphetamine, we found a significant increase in mRNA of a chemokine, CCR2. This increase was accompanied by a significant increase in histone H3 lysine 4 (H3K4) trimethylation at its promoter. Interestingly, the maintenance of sensitization to methamphetamine-induced hyperlocomotion was significantly decreased in CCR2 knockout mice. These findings suggest that increased CCR2 associated with epigenetic modification after the intermittent administration of methamphetamine may be associated with the maintenance of sensitization to methamphetamine-induced hyperlocomotion.