Impact of ambient temperature on hyperthermia induced by (+/-)3,4-methylenedioxymethamphetamine in rhesus macaques.
The ambient temperature (T(A)) 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 T(A) 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 T(A) 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 T(A) conditions (18, 24, and 30 degrees 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 approximately 1 degrees 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 degrees C condition. It is concluded that MDMA produces a similar degree of hyperthermia in rhesus monkeys across a range of T(A) 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.
Von Huben
Stefani N
SN
1Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.
Lay
Christopher C
CC
Crean
Rebecca D
RD
Davis
Sophia A
SA
Katner
Simon N
SN
Taffe
Michael A
MA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005334:Fever / Q000139:chemically induced*; D008253:Macaca mulatta; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D013686:Telemetry; D013696:Temperature
D018817:N-Methyl-3,4-methylenedioxyamphetamine