Pharmacological and behavioral determinants of cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine, and para -methoxyamphetamine-induced hyperthermia

Abstract

Rationale: Cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), and para-methoxyamphetamine (PMA) disrupt normal thermoregulation in humans, with PMA being associated with more severe cases of hyperthermia. Harm minimization advice on how to prevent overheating depends on appropriate thermoregulatory behavior by drug users. Objectives: The purpose of the current study was to establish dose–response relationships for the effects of a number of commonly used illicit stimulants and investigate the behavioral response to increased core temperature. Materials and methods Sprague-Dawley rats with telemetry implants were administered either saline or 4, 12, 26, 40 or 80 μmol/kg of cocaine, methamphetamine, MDMA, or PMA and confined to an ambient temperature of 30°C for 30 min, before being able to choose their preferred temperature on a thermally graded runway (11-41°C). Results: The increased core temperature caused by administration of cocaine, methamphetamine, and MDMA treatment led to the animals seeking the cool end of the runway to correct their core temperature, although this did not occur in PMA-treated rats. The order of potency for increasing core temperature was methamphetamine >PMA = MDMA> cocaine. This differed to the slopes of the dose–response curves where MDMA and PMA showed the steepest slope for the doses used followed by methamphetamine then cocaine. Conclusions: These results suggest that behavioral aspects of thermoregulation are important in assessing the potential of individual drugs to cause harmful increases in core temperature.