Repeated MDMA administration increases MDMA-produced locomotor activity and facilitates the acquisition of MDMA self-administration: role of dopamine D 2 receptor mechanisms.

RATIONALE: Repeated exposure to ±3, 4-methylenedioxymethamphetamine (MDMA) produces sensitization to MDMA-produced hyperactivity, but the mechanisms underlying the development of this sensitized response or the relationship to the reinforcing effects of MDMA is unknown.

OBJECTIVES: This study determined the effect of a sensitizing regimen of MDMA exposure on the acquisition of MDMA self-administration and investigated the role of dopamine D2 receptor mechanisms.

METHODS: Rats received the selective D2 antagonist, eticlopride (0.0 or 0.3 mg/kg, i.p.) and MDMA (0.0 or 10.0 mg/kg, i.p.) during a five-day pretreatment regimen. Two days following the final session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) and the latency to acquisition of MDMA self-administration were determined.

RESULTS: Pretreatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration. Administration of eticlopride during MDMA pretreatment completely blocked the development of sensitization to MDMA-produced hyperactivity but failed to significantly alter the facilitated acquisition of MDMA self-administration. Pretreatment with eticlopride alone facilitated the acquisition of self-administration.

CONCLUSIONS: These data suggest that repeated MDMA exposure sensitized both the locomotor activating and reinforcing effects of MDMA. Activation of D2 receptors during MDMA pretreatment appears critical for the development of sensitization to MDMA-produced hyperactivity. The role of D2 receptor mechanisms in the development of sensitization to the reinforcing effects of MDMA is equivocal.