High Ambient Temperature Facilitates The Acquisition Of 3,4-Methylenedioxymethamphetamine (MDMA) Self-Administration

Abstract

RationaleMDMA alters body temperature in rats with a direction that depends on the ambient temperature (TA). The thermoregulatory effects of MDMA and TA may affect intravenous self-administration (IVSA) of MDMA but limited prior reports conflict.\n\nObjectiveTo determine how body temperature responses under high and low TA influence MDMA IVSA.\n\nMethodsMale Sprague-Dawley rats were trained to IVSA MDMA (1.0 mg/kg/infusion; 2-hr sessions; FR5 schedule of reinforcement) under TA 20{degrees}C or 30{degrees}C. Radiotelemetry transmitters recorded body temperature and activity during IVSA.\n\nResultsMDMA intake increased under both TA during acquisition, but to a greater extent in the 30{degrees}C group. The magnitude of hypothermia was initially equivalent between groups but diminished over training in the 30{degrees}C group. Within-session activity was initially lower in the 30{degrees} C group, but by the end of acquisition and maintenance, activity was similar for both groups. When TA conditions were swapped, the hot-trained group increased MDMA IVSA under 20 {degrees}C TA and a modest decrease in drug intake was observed in the cold-trained group under 30 {degrees}C TA. 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 TA increased intracranial self-stimulation thresholds in a different group of rats and MDMA reduced thresholds below baseline at low, but not high, TA.\n\nConclusionsHigh TA appears to enhance acquisition of MDMA IVSA through an aversive effect and not via thermoregulatory motivation.