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Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat.
J Neurosci 1998; 18(13):5086-94JN

Abstract

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of abuse and has been shown to be neurotoxic to 5-HT terminals in many species. MDMA-engendered neurotoxicity has been shown to be affected by both ambient temperature and core body temperature. We now report that small (2 degreesC) changes in ambient temperature produce changes in core temperature in MDMA-treated rats, but the same changes in ambient temperature do not affect core temperature of saline-treated animals. Furthermore, increases in core temperature of MDMA-treated animals increase neurotoxicity. Rats were given MDMA (20 or 40 mg/kg) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28, or 30 degreesC using a novel temperature measurement apparatus that controls ambient temperature +/-0.5 degrees C. Two weeks after MDMA treatment, the rats were killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were analyzed as a measure of neurotoxicity. Rats treated with MDMA at 20 and 22 degrees C showed a hypothermic core temperature response. Treatment with MDMA at 28 and 30 degreesC produced a hyperthermic response. At ambient temperatures of 20-24 degrees C, neurotoxicity was not observed in the frontal cortex, somatosensory cortex, hippocampus, or striatum. At ambient temperatures of 26-30 degrees C, neurotoxicity was seen and correlated with core temperature in all regions examined. These data indicate that ambient temperature has a significant affect on MDMA neurotoxicity, core temperature, and thermoregulation in rats. This finding has implications on both the temperature dependence of the mechanism of MDMA neurotoxicity and human use because fatal hyperthermia is associated with MDMA use in humans.

Authors+Show Affiliations

University of Chicago, Department of Pharmacological and Physiological Sciences, Chicago, Illinois 60637, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9634574

Citation

Malberg, J E., and L S. Seiden. "Small Changes in Ambient Temperature Cause Large Changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced Serotonin Neurotoxicity and Core Body Temperature in the Rat." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 18, no. 13, 1998, pp. 5086-94.
Malberg JE, Seiden LS. Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. J Neurosci. 1998;18(13):5086-94.
Malberg, J. E., & Seiden, L. S. (1998). Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 18(13), pp. 5086-94.
Malberg JE, Seiden LS. Small Changes in Ambient Temperature Cause Large Changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced Serotonin Neurotoxicity and Core Body Temperature in the Rat. J Neurosci. 1998 Jul 1;18(13):5086-94. PubMed PMID: 9634574.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Small changes in ambient temperature cause large changes in 3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core body temperature in the rat. AU - Malberg,J E, AU - Seiden,L S, PY - 1998/6/23/pubmed PY - 1998/6/23/medline PY - 1998/6/23/entrez SP - 5086 EP - 94 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 18 IS - 13 N2 - The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of abuse and has been shown to be neurotoxic to 5-HT terminals in many species. MDMA-engendered neurotoxicity has been shown to be affected by both ambient temperature and core body temperature. We now report that small (2 degreesC) changes in ambient temperature produce changes in core temperature in MDMA-treated rats, but the same changes in ambient temperature do not affect core temperature of saline-treated animals. Furthermore, increases in core temperature of MDMA-treated animals increase neurotoxicity. Rats were given MDMA (20 or 40 mg/kg) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28, or 30 degreesC using a novel temperature measurement apparatus that controls ambient temperature +/-0.5 degrees C. Two weeks after MDMA treatment, the rats were killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were analyzed as a measure of neurotoxicity. Rats treated with MDMA at 20 and 22 degrees C showed a hypothermic core temperature response. Treatment with MDMA at 28 and 30 degreesC produced a hyperthermic response. At ambient temperatures of 20-24 degrees C, neurotoxicity was not observed in the frontal cortex, somatosensory cortex, hippocampus, or striatum. At ambient temperatures of 26-30 degrees C, neurotoxicity was seen and correlated with core temperature in all regions examined. These data indicate that ambient temperature has a significant affect on MDMA neurotoxicity, core temperature, and thermoregulation in rats. This finding has implications on both the temperature dependence of the mechanism of MDMA neurotoxicity and human use because fatal hyperthermia is associated with MDMA use in humans. SN - 0270-6474 UR - https://www.unboundmedicine.com/medline/citation/9634574/Small_changes_in_ambient_temperature_cause_large_changes_in_34_methylenedioxymethamphetamine__MDMA__induced_serotonin_neurotoxicity_and_core_body_temperature_in_the_rat_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=9634574 DB - PRIME DP - Unbound Medicine ER -