Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys

Abstract

MDMA produces an acute hyperthermia in unrestrained rhesus monkeys, much as it does with rats, mice, pigs, rabbits and humans. Hyperthermia occurs despite no increase in locomotor activity thus the effect does not depend on motor activation. Each enantiomer appears to be equivalently active thus primates may differ from rodents in thermoregulatory sensitivity to the R(-) enantiomer. Significant differences in outcome between this and a prior study in monkeys indicate a need for additional study of the thermoregulatory impact of MDMA in nonhuman primates.

Impact of Ambient Temperature on Hyperthermia Induced by (±)3,4-Methylenedioxymethamphetamine in Rhesus Macaques

“…Post hoc comparisons confirmed significant increases over vehicle for the 1.0-2.4 mg/kg doses at 181C T A and for the 2.4 mg/kg dose at either 241C T A or 301C T A . Activity patterns were highly consistent with our prior report (Taffe et al, 2005) with activity levels being highest at the time of injection and thereafter decreasing to low levels for up to 3 h after injection. These patterns were nearly identical across all treatment conditions, including vehicle.…”

“…The overall implication of this work is that while smaller bodied mammals may be protected from MDMA-induced temperature elevations below B201C, this is unlikely to be the case for macaque monkeys or humans. These data also extend our initial study (Taffe et al, 2005) by demonstrating that the monkeys develop approximately equivalent changes in body temperature following a recreationally relevant range of MDMA doses (0.56-2.4 mg/kg). Reassuringly, the data suggest that comparisons made between the results of prior monkey neurotoxicity studies are unlikely to be substantially affected by the wide range of 'normal' ambient temperatures (B21-271C) under which they have been conducted.…”

“…Four additional individuals not on the relevant protocol remained in the room for the ambient temperature studies by decision of the Attending Veterinarian following consideration of all aspects of animal well-being. These latter four animals had previously participated in a prior series of challenges with MDMA encompassing no more than eight doses of racemic MDMA or either enantiomer, administered at a dose of 1.7 mg/kg, generally intramuscularly but at least once each p.o., at 1-to 2-week intervals (Taffe et al, 2005).…”

“…The recreationally abused drug (7)3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') elevates body temperature in rats (Brown and Kiyatkin, 2004;Dafters, 1994;Malberg and Seiden, 1998), mice (Carvalho et al, 2002;Fantegrossi et al, 2003), guinea-pigs (Saadat et al, 2004), pigs (Fiege et al, 2003;Rosa-Neto et al, 2004), rabbits (Pedersen and Blessing, 2001), humans (Freedman et al, 2005), and rhesus macaques (Taffe et al, 2005). Sufficiently low ambient temperature conditions can prevent (7)MDMA from inducing hyperthermia or even result in hypothermia in rodent models (Dafters, 1994;Gordon et al, 1991;Miller and O'Callaghan, 1994).…”

“…We have recently established that an intramuscular dose of 1.7 mg/kg of (7)MDMA, or either enantiomer, administered under T A of 23-241C in unrestrained rhesus monkeys elevates body temperature without significant increases in locomotor activity (Taffe et al, 2005). Interestingly, Freedman et al (2005) have shown that body temperature is elevated in human volunteers after 2.0 mg/kg (7)MDMA per os and that this effect is similar under T A of 18 or 301C.…”