MDMA self‐administration in rats: acquisition, progressive ratio responding and serotonin transporter binding

Abstract

Abstract 3,4‐Methylenedioxymethamphetamine (MDMA) self‐administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug‐naïve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self‐administration was measured during daily 6‐h sessions. Dose–effect data were obtained for MDMA (0.25–1.0 mg/kg/infusion) self‐administration under a progressive ratio (PR) schedule of reinforcement. The effect of experimenter‐ or self‐administered MDMA on [ 3 H] paroxetine binding in several brain regions was measured. Acquisition of MDMA self‐administration was highly variable and not different for 0.25 or 1.0 mg/kg/infusion progressed with approximately 60% of the rats acquiring reliable self‐administration during the 15‐day test period. The percentage of rats that acquired MDMA self‐administration was lower than the percentage of rats that acquired cocaine (0.5 mg/kg/infusion) self‐administration, and cocaine self‐administration was acquired with a shorter latency. Responding maintained by MDMA was dose dependent, and breakpoints under a PR schedule increased with dose. Radioligand binding and autoradiography demonstrated lower densities of serotonin transporter sites (SERT) in MDMA self‐administering rats as compared with controls across brain regions. The reduction in SERT densities was comparable in magnitude to rats treated with experimenter‐administered doses of MDMA. These data support the idea that MDMA is a drug with high abuse liability, and long‐term self‐administration may lead to long‐lasting deficits in serotonin neurotransmission.