High ambient temperature facilitates the acquisition of 3,4-methylenedioxymethamphetamine (MDMA) self-administration

Abstract Rationale MDMA alters body temperature in rats with a direction that depends on the ambient temperature (T A ). The thermoregulatory effects of MDMA and T A may affect intravenous self-administration (IVSA) of MDMA but limited prior reports conflict.

Objective: To determine how body temperature responses under high and low T A influence MDMA IVSA.

Methods: Male Sprague-Dawley rats were trained to IVSA MDMA (1.0 mg/kg/infusion; 2-hr sessions; FR5 schedule of reinforcement) under T A 20°C or 30°C. Radiotelemetry transmitters recorded body temperature and activity during IVSA.

Results: MDMA intake increased under both T A during acquisition, but to a greater extent in the 30°C group. The magnitude of hypothermia was initially equivalent between groups but diminished over training in the 30°C group. Within-session activity was initially lower in the 30° C group, but by the end of acquisition and maintenance, activity was similar for both groups. When T A conditions were swapped, the hot-trained group increased MDMA IVSA under 20 °C T A and a modest decrease in drug intake was observed in the cold-trained group under 30 °C T A . Subsequent non-contingent MDMA (1.0-5.0 mg/kg, i.v.) found that rats with higher MDMA IVSA rates showed blunted hypothermia compared with rats with lower IVSA levels; however, within-session activity did not differ by group. High T A increased intracranial self-stimulation thresholds in a different group of rats and MDMA reduced thresholds below baseline at low, but not high, T A .

Conclusions: High T A appears to enhance acquisition of MDMA IVSA through an aversive effect and not via thermoregulatory motivation.