Effects of 3,4-methylenedioxymethamphetamine and related amphetamines on autonomic and behavioral thermoregulation

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and related amphetamines such as para-methoxyamphetamine (PMA) disrupt normal thermoregulation in humans and rats. Behavior, an important component of thermoregulation in mammals, has not been investigated with respect to these drugs. This is surprising as harm minimization depends on appropriate thermoregulatory behavior by drug users. The effects of MDMA (10 mg/kg), PMA (10 mg/kg) and d-amphetamine (2 mg/kg) were therefore studied in Sprague-Dawley rats, with telemetry implants measuring core body temperature (TC), locomotor activity and heart rate. Rats were administered an amphetamine or saline and confined to an ambient temperature of 21, 30 or 15 °C for 30 min, before being able to choose their preferred temperature (TP) on a thermally graded runway (11-41 °C). Confinement at 21 °C had little effect on TC in any group. At 30 °C MDMA and PMA increased TC compared to saline (p < 0.001). MDMA treated animals behaviorally overcompensated for this effect (p <  0.01). Locomotor activity after MDMA treatment was significantly elevated compared with saline (p < 0.01). In contrast, at 15 °C MDMA administration resulted in a lower TC than saline (p < 0.001). MDMA and PMA disrupt autonomic components of thermoregulation, while behavioral components are disrupted to a lesser extent. These results highlight differences in thermoregulatory responses to individual drugs, which were only evident when behavior was measured, and this may be important in assessing their risk.