Intravenous methamphetamine self-administration in rats: Effects of intravenous or intraperitoneal MDMA co-administration

The combined use of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') with methamphetamine (METH) by recreational drug users is of particular concern due to their similar pharmacological and toxic profiles. In the current study we sought to elucidate why combining these particular drugs is such a popular choice among party-drug users. This was investigated through characterisation of the possible interactive effects of MDMA on METH intravenous self-administration. The first experiment involved characterisation of the METH dose-response curve for intravenous self-administration. Male Hooded-Wistar rats were trained to self-administer intravenous METH (0.01-0.3 mg/kg/infusion) and an inverted-U dose-response curve was obtained. In Experiment 2, a second squad of rats self-administered 0.01, 0.03 or 0.1 mg/kg/infusion METH and had small amounts of MDMA (0.001-0.03 mg/kg) then introduced into the infusion solution. Addition of MDMA to the METH infusion solution resulted in a dose independent reduction in responding. In Experiment 3, a third squad of rats was treated 20 min pre-session with an intraperitoneal injection of saline, 1.25 or 2.5 mg/kg of MDMA or METH to evaluate whether the reduction in responding evident in Experiment 2 was due to an MDMA-induced decrease in locomotor activity. Pre-treatment with intraperitoneal MDMA or METH had no effect on METH self-administration nor activity. We hypothesise that the reduction in METH self-administration caused by MDMA may reflect inhibitory effects of MDMA-induced 5-HT release on dopaminergic mechanisms.