Rewarding effects of 3,4-methylenedioxymethamphetamine (“Ecstasy”) in dominant and subordinate OF-1 mice in the place preference conditioning paradigm

Abstract

We tested the ability of 3,4-methylenedioxymethamphetamine (MDMA) to induce conditioned place preference (CPP) in dominant and subordinate OF-1 mice subjected to cohabitation and repeated sessions of agonistic confrontation, as well as in non-confronted mice. We selected doses of MDMA (2, 6, 10 mg/kg) previously reported to induce CPP in mice and we measured expression of c-Fos evoked by the treatments in non-confronted mice. MDMA induced c-Fos protein in several corticolimbic regions involved in drug-induced reward. Mice were exposed to brief sessions of agonistic confrontation on 5 consecutive days. Determinations of circulating hormones and drug conditioning tests were carried out on completion of the encounters. The results of hormone assays indicated that dominant mice had higher serum concentrations of testosterone, but lower levels of corticosterone, than submissive mice. Post-conditioning tests after drug conditioning (4 injections of MDMA or saline on alternate days) showed that MDMA significantly produced CPP at doses of 2 and 6 mg/kg, but not at 10 mg/kg, an inverted U-shaped pattern of conditioning that was invariable in non-confronted, dominant and subordinate mice. These results demonstrate that the endocrine and behavioural correlates linked to social status and social stress in mice are not paralleled by significant changes in the rewarding efficacy of MDMA in the CPP paradigm under the specific conditions tested.