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

In rats, high ambient temperature (30°C) increases the acquisition of intravenous self-administration of MDMA more than low temperature (20°C). Initially, MDMA caused similar hypothermia in both temperature groups, but this effect diminished over training in the hot group. Activity levels, initially lower in the hot group, became similar by the end of training. When temperature conditions were swapped, rats trained in the hot condition increased MDMA intake under cold, while those trained in the cold modestly decreased intake under hot. Rats with higher MDMA intake showed blunted hypothermia after non-contingent MDMA. High temperature alone raised brain reward thresholds, and MDMA lowered thresholds below baseline only at low temperature. The findings suggest that high temperature enhances MDMA self-administration acquisition through an aversive effect rather than thermoregulatory motivation.

Study at a glance

Abstract

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.