Original Article
Neuropsychopharmacology (2007) 32, 673–681. doi:10.1038/sj.npp.1301078; published online 12 April 2006
Impact of Ambient Temperature on Hyperthermia Induced by (
)3,4-Methylenedioxymethamphetamine in Rhesus Macaques
Stefani N Von Huben1, Christopher C Lay1, Rebecca D Crean1, Sophia A Davis1, Simon N Katner1 and Michael A Taffe1
1Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA
Correspondence: Dr MA Taffe, Molecular and Integrative Neurosciences Department, SP30-2400, 10550 North Torrey Pines Road, The Scripps Research Institute, La Jolla, CA 92037, USA. Tel: +1 858 784 7228; Fax: +1 858 784 7405; E-mail: mtaffe@scripps.edu
Received 30 January 2006; Revised 27 February 2006; Accepted 6 March 2006; Published online 12 April 2006.
Abstract
The ambient temperature (TA) under which rodents are exposed to (
)3,4-methylenedioxymethamphetamine (MDMA) affects the direction and magnitude of the body temperature response, and the degree of hypo/hyperthermia generated in subjects can modify the severity of lasting brain changes in 'neurotoxicity' models. The thermoregulatory effects of MDMA have not been well described in non-human primates and it is unknown if TA has the potential to affect acute hyperthermia and therefore other lasting consequences of MDMA. The objective of this study was to determine if the temperature alteration produced by MDMA in nonhuman primates depends on TA as it does in rats and mice. Body temperature and spontaneous home cage activity were monitored continuously in six male rhesus monkeys via radiotelemetry. The subjects were challenged intramuscularly with 0.56–2.4 mg/kg (
)MDMA under each of three TA conditions (18, 24, and 30°C) in a randomized order. The temperature was significantly elevated following injection with all doses of MDMA under each ambient temperature. The magnitude of mean temperature change was
1°C in most conditions suggesting a closely controlled thermoregulatory response in monkeys across a range of doses and ambient temperatures. Activity levels were generally suppressed by MDMA; however, a 50% increase over vehicle was observed after 0.56 MDMA under the 30°C condition. It is concluded that MDMA produces a similar degree of hyperthermia in rhesus monkeys across a range of TA conditions that result in hypothermia or exaggerated hyperthermia in rodents. Monkey temperature responses to MDMA appear to be more similar to humans than to rodents and therefore the monkey may offer an improved model of effects related to MDMA-induced hyperthermia.
Keywords:
(
)MDMA, Macaca mulatta, circadian, thermoregulation, serotonin
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