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Effects of social interaction and warm ambient temperature on brain hyperthermia induced by the designer drugs methylone and MDPV.
Neuropsychopharmacology 2015; 40(2):436-45N

Abstract

3,4-Methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV) are new drugs of abuse that have gained worldwide popularity. These drugs are structurally similar to 3,4-methylenedioxymethamphetamine (MDMA) and share many of its physiological and behavioral effects in humans, including the development of hyperthermia during acute intoxication. Here, we examined the effects of methylone (1-9 mg/kg, s.c.) or MDPV (0.1-1.0 mg/kg, s.c.) on brain temperature homeostasis in rats maintained in a standard laboratory environment (single-housed in a quiet rest at 22 °C) and under conditions that model human drug use (social interaction and 29 °C ambient temperature). By simultaneously monitoring temperatures in the nucleus accumbens, temporal muscle, and facial skin, we assessed the effects of methylone and MDPV on intra-brain heat production and cutaneous vascular tone, two critical factors that control brain temperature responses. Both methylone and MDPV dose-dependently increased brain temperature, but even at high doses that induced robust locomotor activation, hyperthermia was modest in magnitude (up to ∼2 °C). Both drugs also induced dose-dependent peripheral vasoconstriction, which appears to be a primary mechanism determining the brain hyperthermic responses. In contrast to the powerful potentiation of MDMA-induced hyperthermia by social interaction and warm ambient temperature, such potentiation was absent for methylone and minimal for MDPV. Taken together, despite structural similarities to MDMA, exposure to methylone or MDPV under conditions commonly associated with human drug use does not lead to profound elevations in brain temperature and sustained vasoconstriction, two critical factors associated with MDMA toxicity.

Authors+Show Affiliations

Intramural Research Program, NIDA-NIH, Baltimore, MD, USA.Intramural Research Program, NIDA-NIH, Baltimore, MD, USA.Intramural Research Program, NIDA-NIH, Baltimore, MD, USA.Intramural Research Program, NIDA-NIH, Baltimore, MD, USA.Intramural Research Program, NIDA-NIH, Baltimore, MD, USA.

Pub Type(s)

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

Language

eng

PubMed ID

25074640

Citation

Kiyatkin, Eugene A., et al. "Effects of Social Interaction and Warm Ambient Temperature On Brain Hyperthermia Induced By the Designer Drugs Methylone and MDPV." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 40, no. 2, 2015, pp. 436-45.
Kiyatkin EA, Kim AH, Wakabayashi KT, et al. Effects of social interaction and warm ambient temperature on brain hyperthermia induced by the designer drugs methylone and MDPV. Neuropsychopharmacology. 2015;40(2):436-45.
Kiyatkin, E. A., Kim, A. H., Wakabayashi, K. T., Baumann, M. H., & Shaham, Y. (2015). Effects of social interaction and warm ambient temperature on brain hyperthermia induced by the designer drugs methylone and MDPV. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 40(2), pp. 436-45. doi:10.1038/npp.2014.191.
Kiyatkin EA, et al. Effects of Social Interaction and Warm Ambient Temperature On Brain Hyperthermia Induced By the Designer Drugs Methylone and MDPV. Neuropsychopharmacology. 2015;40(2):436-45. PubMed PMID: 25074640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of social interaction and warm ambient temperature on brain hyperthermia induced by the designer drugs methylone and MDPV. AU - Kiyatkin,Eugene A, AU - Kim,Albert H, AU - Wakabayashi,Ken T, AU - Baumann,Michael H, AU - Shaham,Yavin, Y1 - 2014/07/30/ PY - 2014/06/04/received PY - 2014/07/24/revised PY - 2014/07/25/accepted PY - 2014/7/31/entrez PY - 2014/7/31/pubmed PY - 2015/12/19/medline SP - 436 EP - 45 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 40 IS - 2 N2 - 3,4-Methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV) are new drugs of abuse that have gained worldwide popularity. These drugs are structurally similar to 3,4-methylenedioxymethamphetamine (MDMA) and share many of its physiological and behavioral effects in humans, including the development of hyperthermia during acute intoxication. Here, we examined the effects of methylone (1-9 mg/kg, s.c.) or MDPV (0.1-1.0 mg/kg, s.c.) on brain temperature homeostasis in rats maintained in a standard laboratory environment (single-housed in a quiet rest at 22 °C) and under conditions that model human drug use (social interaction and 29 °C ambient temperature). By simultaneously monitoring temperatures in the nucleus accumbens, temporal muscle, and facial skin, we assessed the effects of methylone and MDPV on intra-brain heat production and cutaneous vascular tone, two critical factors that control brain temperature responses. Both methylone and MDPV dose-dependently increased brain temperature, but even at high doses that induced robust locomotor activation, hyperthermia was modest in magnitude (up to ∼2 °C). Both drugs also induced dose-dependent peripheral vasoconstriction, which appears to be a primary mechanism determining the brain hyperthermic responses. In contrast to the powerful potentiation of MDMA-induced hyperthermia by social interaction and warm ambient temperature, such potentiation was absent for methylone and minimal for MDPV. Taken together, despite structural similarities to MDMA, exposure to methylone or MDPV under conditions commonly associated with human drug use does not lead to profound elevations in brain temperature and sustained vasoconstriction, two critical factors associated with MDMA toxicity. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/25074640/Effects_of_social_interaction_and_warm_ambient_temperature_on_brain_hyperthermia_induced_by_the_designer_drugs_methylone_and_MDPV_ L2 - http://dx.doi.org/10.1038/npp.2014.191 DB - PRIME DP - Unbound Medicine ER -