Tags

Type your tag names separated by a space and hit enter

Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys.
Drug Alcohol Depend 2006; 82(3):276-81DA

Abstract

BACKGROUND

Exposure to (+/-)3,4-methylenedioxymethamphetamine ((+/-)MDMA) results in lasting reductions of many markers for serotonin terminals in a range of species. In rodents, the severity of insult depends in large part on the generation of hyperthermia in the subject. (+/-)MDMA can produce either hyperthermia or hypothermia in rodents depending on the ambient temperature and these effects may be limited to the S(+) enantiomer. Limited prior evidence suggests (+/-)MDMA does not produce hyperthermia in chair-restrained monkeys [Bowyer, J.F., Young, J.F., Slikker, W., Itzak, Y., Mayorga, A.J., Newport, G.D., Ali, S.F., Frederick, D.L., Paule, M.G., 2003. Plasma levels of parent compound and metabolites after doses of either d-fenfluramine or d-3,4-methylenedioxymethamphetamine (MDMA) that produce long-term serotonergic alterations. Neurotoxicology 24, 379-390]. This study was therefore conducted to determine if racemic MDMA and its enantiomers induce hyperthermia and increase spontaneous locomotor activity in unrestrained rhesus monkeys.

METHODS

Body temperature and spontaneous home cage activity were monitored continuously in four monkeys via radiotelemetric devices. The subjects were challenged with 1.7 mg/kg, i.m., (+/-)MDMA, S(+)MDMA and R(-)MDMA in pseudorandomized order.

RESULTS

Maximum and average temperature in the 4h interval post-dosing was elevated 0.7-0.9 degrees C by (+/-)MDMA and each enantiomer. Reductions in locomotor activity following dosing did not reliably differ from vehicle effects.

CONCLUSIONS

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.

Authors+Show Affiliations

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. mtaffe@scripps.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16289931

Citation

Taffe, Michael A., et al. "Hyperthermia Induced By 3,4-methylenedioxymethamphetamine in Unrestrained Rhesus Monkeys." Drug and Alcohol Dependence, vol. 82, no. 3, 2006, pp. 276-81.
Taffe MA, Lay CC, Von Huben SN, et al. Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys. Drug Alcohol Depend. 2006;82(3):276-81.
Taffe, M. A., Lay, C. C., Von Huben, S. N., Davis, S. A., Crean, R. D., & Katner, S. N. (2006). Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys. Drug and Alcohol Dependence, 82(3), pp. 276-81.
Taffe MA, et al. Hyperthermia Induced By 3,4-methylenedioxymethamphetamine in Unrestrained Rhesus Monkeys. Drug Alcohol Depend. 2006 May 20;82(3):276-81. PubMed PMID: 16289931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hyperthermia induced by 3,4-methylenedioxymethamphetamine in unrestrained rhesus monkeys. AU - Taffe,Michael A, AU - Lay,Christopher C, AU - Von Huben,Stefani N, AU - Davis,Sophia A, AU - Crean,Rebecca D, AU - Katner,Simon N, Y1 - 2005/11/11/ PY - 2005/08/05/received PY - 2005/09/23/revised PY - 2005/09/30/accepted PY - 2005/11/18/pubmed PY - 2006/10/6/medline PY - 2005/11/18/entrez SP - 276 EP - 81 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 82 IS - 3 N2 - BACKGROUND: Exposure to (+/-)3,4-methylenedioxymethamphetamine ((+/-)MDMA) results in lasting reductions of many markers for serotonin terminals in a range of species. In rodents, the severity of insult depends in large part on the generation of hyperthermia in the subject. (+/-)MDMA can produce either hyperthermia or hypothermia in rodents depending on the ambient temperature and these effects may be limited to the S(+) enantiomer. Limited prior evidence suggests (+/-)MDMA does not produce hyperthermia in chair-restrained monkeys [Bowyer, J.F., Young, J.F., Slikker, W., Itzak, Y., Mayorga, A.J., Newport, G.D., Ali, S.F., Frederick, D.L., Paule, M.G., 2003. Plasma levels of parent compound and metabolites after doses of either d-fenfluramine or d-3,4-methylenedioxymethamphetamine (MDMA) that produce long-term serotonergic alterations. Neurotoxicology 24, 379-390]. This study was therefore conducted to determine if racemic MDMA and its enantiomers induce hyperthermia and increase spontaneous locomotor activity in unrestrained rhesus monkeys. METHODS: Body temperature and spontaneous home cage activity were monitored continuously in four monkeys via radiotelemetric devices. The subjects were challenged with 1.7 mg/kg, i.m., (+/-)MDMA, S(+)MDMA and R(-)MDMA in pseudorandomized order. RESULTS: Maximum and average temperature in the 4h interval post-dosing was elevated 0.7-0.9 degrees C by (+/-)MDMA and each enantiomer. Reductions in locomotor activity following dosing did not reliably differ from vehicle effects. CONCLUSIONS: 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. SN - 0376-8716 UR - https://www.unboundmedicine.com/medline/citation/16289931/Hyperthermia_induced_by_34_methylenedioxymethamphetamine_in_unrestrained_rhesus_monkeys_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(05)00301-7 DB - PRIME DP - Unbound Medicine ER -