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Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced by MDMA (Ecstasy) under conditions that mimic human drug use.
J Neurosci 2014; 34(23):7754-62JN

Abstract

MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave" parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22-23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ~1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues.

Authors+Show Affiliations

Intramural Research Program, National Institute on Drug Abuse-National Institutes of Health, Baltimore, Maryland 21224 ekiyatki@intra.nida.nih.gov.Intramural Research Program, National Institute on Drug Abuse-National Institutes of Health, Baltimore, Maryland 21224.Intramural Research Program, National Institute on Drug Abuse-National Institutes of Health, Baltimore, Maryland 21224.Intramural Research Program, National Institute on Drug Abuse-National Institutes of Health, Baltimore, Maryland 21224.Intramural Research Program, National Institute on Drug Abuse-National Institutes of Health, Baltimore, Maryland 21224.

Pub Type(s)

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

Language

eng

PubMed ID

24899699

Citation

Kiyatkin, Eugene A., et al. "Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced By MDMA (Ecstasy) Under Conditions That Mimic Human Drug Use." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 34, no. 23, 2014, pp. 7754-62.
Kiyatkin EA, Kim AH, Wakabayashi KT, et al. Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced by MDMA (Ecstasy) under conditions that mimic human drug use. J Neurosci. 2014;34(23):7754-62.
Kiyatkin, E. A., Kim, A. H., Wakabayashi, K. T., Baumann, M. H., & Shaham, Y. (2014). Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced by MDMA (Ecstasy) under conditions that mimic human drug use. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 34(23), pp. 7754-62. doi:10.1523/JNEUROSCI.0506-14.2014.
Kiyatkin EA, et al. Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced By MDMA (Ecstasy) Under Conditions That Mimic Human Drug Use. J Neurosci. 2014 Jun 4;34(23):7754-62. PubMed PMID: 24899699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Critical role of peripheral vasoconstriction in fatal brain hyperthermia induced by MDMA (Ecstasy) under conditions that mimic human drug use. AU - Kiyatkin,Eugene A, AU - Kim,Albert H, AU - Wakabayashi,Ken T, AU - Baumann,Michael H, AU - Shaham,Yavin, PY - 2014/6/6/entrez PY - 2014/6/6/pubmed PY - 2014/7/26/medline KW - MDMA KW - acute intoxication KW - brain temperature KW - peripheral vasoconstriction KW - social interaction KW - warm environment SP - 7754 EP - 62 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 34 IS - 23 N2 - MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave" parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22-23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ~1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/24899699/Critical_role_of_peripheral_vasoconstriction_in_fatal_brain_hyperthermia_induced_by_MDMA__Ecstasy__under_conditions_that_mimic_human_drug_use_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=24899699 DB - PRIME DP - Unbound Medicine ER -