Differential changes in mesolimbic dopamine following contingent and non-contingent MDMA self-administration in mice

Abstract

Rationale: There is evidence demonstrating changes in dopamine (DA) transmission in the nucleus accumbens (NAc) related to contingent versus non-contingent drug administration.

Objectives: The aim of this study was to evaluate basal and 3,4-methylenedioxymethamphetamine (MDMA)-stimulated DA levels in the NAc of mice that had previously received contingent and non-contingent infusions of MDMA. Contingent mice were trained to self-administer MDMA (0.125 mg/kg/infusion) in 2-h sessions for 10 days. Yoked mice received either MDMA at the same dose or saline. Forty-eight hours after the last MDMA or saline administration, DA levels were measured by in vivo microdialysis before and after an MDMA (10 mg/kg, i.p.) challenge. Binding of [(3)H]-mazindol and [(3)H]-citalopram was evaluated by autoradiography.

Results: Animals receiving MDMA infusions showed significantly lower basal DA levels than the yoked saline group. A reduced activation of DA was observed following MDMA in contingent mice with respect to both yoked MDMA and saline mice. No significant alterations in DA transporter or serotonin transporter were observed in the three groups of mice.

Conclusions: These results suggest that prolonged exposure to MDMA in mice produces changes in basal DA levels after drug withdrawal and a decreased neurochemical response at the level of the mesolimbic DA reward pathway that is, in part, related to instrumental learning during self-administration.