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 [3H] 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.
The ability of benzylpiperazine (BZP) to substitute for cocaine and to initiate self-administration in drug-naive subjects was assessed to determine whether BZP has abuse liability. Further, the effects of a pretreatment with dopamine D1-like receptor antagonist (SCH23390) were examined to elucidate the mechanisms associated with BZP reward. First, the ability for BZP (0.125, 0.25 and 0.5 mg/kg/infusion) to substitute for cocaine self-administration was assessed, and the acquisition of BZP (0.5 mg/kg/infusion) self-administration by drug-naive and untrained rats was determined during a 15-day period. Subsequently, dose-effect curves for cocaine (0.06, 0.125, 0.25 or 0.5 mg/kg/infusion) and BZP self-administration (0.125, 0.25, 0.5 or 1.0 mg/kg/infusion) and the effect of SCH23390 (0.00 or 0.02 mg/kg) on BZP and cocaine self-administration were examined. BZP substituted for cocaine, and drug-naive rats rapidly acquired BZP self-administration. BZP self-administration was maintained by a more restricted range of doses than was cocaine self-administration, and responding maintained by BZP was sensitive to dopamine antagonism. The present findings indicate that BZP self-administration, like cocaine self-administration, is readily acquired and mediated by dopaminergic mechanisms.
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