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Chronic stress enhances the corticosterone response and neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the role of ambient temperature.
J Pharmacol Exp Ther. 2010 Oct; 335(1):180-9.JP

Abstract

Stress facilitates drug abuse by humans. In rodents, stress enhances the neurochemical, neuroendocrine, and behavioral responses to psychostimulants. Although chronic unpredictable stress (CUS) enhances the acute hyperthermic and long-term monoamine-depleting effects of the psychostimulant +3,4-methylenedioxymethamphetamine (MDMA), the roles of hyperthermia and corticosterone (CORT) in mediating the stress-induced enhancement of MDMA-induced serotonin (5-HT) and dopamine (DA) depletions are unknown. Rats were exposed to 10 days of CUS and then challenged with MDMA (5 mg/kg i.p. once every 2 h for a total of four injections). Prior exposure to CUS augmented MDMA-induced hyperthermia and plasma CORT secretion and the long-term depletions in 5-HT content in striatum, hippocampus, and frontal cortex and DA content in striatum. A reduced ambient temperature of 21°C attenuated the hyperthermia, CORT secretion, and 5-HT decreases after MDMA in nonstressed rats. The lower ambient temperature also prevented the augmented hyperthermia, CORT secretion, and enhanced 5-HT and DA depletions after MDMA in chronically stressed rats to levels exhibited by nonstressed, MDMA-treated rats. To investigate the role of CORT on monoamine depletions in response to MDMA, stressed and nonstressed rats were treated with the CORT synthesis inhibitor metyrapone during exposure to MDMA. Metyrapone prevented CORT secretion in both stressed and nonstressed rats but did not modify 5-HT or DA depletions in any brain region examined. This study suggests that enhanced CORT is a consequence of enhanced hyperthermia and the CUS-induced enhancements of MDMA-induced monoamine depletions may be mediated by hyperthermia but not CORT.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20634423

Citation

Johnson, Bethann N., and Bryan K. Yamamoto. "Chronic Stress Enhances the Corticosterone Response and Neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the Role of Ambient Temperature." The Journal of Pharmacology and Experimental Therapeutics, vol. 335, no. 1, 2010, pp. 180-9.
Johnson BN, Yamamoto BK. Chronic stress enhances the corticosterone response and neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the role of ambient temperature. J Pharmacol Exp Ther. 2010;335(1):180-9.
Johnson, B. N., & Yamamoto, B. K. (2010). Chronic stress enhances the corticosterone response and neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the role of ambient temperature. The Journal of Pharmacology and Experimental Therapeutics, 335(1), 180-9. https://doi.org/10.1124/jpet.110.171322
Johnson BN, Yamamoto BK. Chronic Stress Enhances the Corticosterone Response and Neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the Role of Ambient Temperature. J Pharmacol Exp Ther. 2010;335(1):180-9. PubMed PMID: 20634423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic stress enhances the corticosterone response and neurotoxicity to +3,4-methylenedioxymethamphetamine (MDMA): the role of ambient temperature. AU - Johnson,Bethann N, AU - Yamamoto,Bryan K, Y1 - 2010/07/15/ PY - 2010/7/17/entrez PY - 2010/7/17/pubmed PY - 2010/10/22/medline SP - 180 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 335 IS - 1 N2 - Stress facilitates drug abuse by humans. In rodents, stress enhances the neurochemical, neuroendocrine, and behavioral responses to psychostimulants. Although chronic unpredictable stress (CUS) enhances the acute hyperthermic and long-term monoamine-depleting effects of the psychostimulant +3,4-methylenedioxymethamphetamine (MDMA), the roles of hyperthermia and corticosterone (CORT) in mediating the stress-induced enhancement of MDMA-induced serotonin (5-HT) and dopamine (DA) depletions are unknown. Rats were exposed to 10 days of CUS and then challenged with MDMA (5 mg/kg i.p. once every 2 h for a total of four injections). Prior exposure to CUS augmented MDMA-induced hyperthermia and plasma CORT secretion and the long-term depletions in 5-HT content in striatum, hippocampus, and frontal cortex and DA content in striatum. A reduced ambient temperature of 21°C attenuated the hyperthermia, CORT secretion, and 5-HT decreases after MDMA in nonstressed rats. The lower ambient temperature also prevented the augmented hyperthermia, CORT secretion, and enhanced 5-HT and DA depletions after MDMA in chronically stressed rats to levels exhibited by nonstressed, MDMA-treated rats. To investigate the role of CORT on monoamine depletions in response to MDMA, stressed and nonstressed rats were treated with the CORT synthesis inhibitor metyrapone during exposure to MDMA. Metyrapone prevented CORT secretion in both stressed and nonstressed rats but did not modify 5-HT or DA depletions in any brain region examined. This study suggests that enhanced CORT is a consequence of enhanced hyperthermia and the CUS-induced enhancements of MDMA-induced monoamine depletions may be mediated by hyperthermia but not CORT. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/20634423/Chronic_stress_enhances_the_corticosterone_response_and_neurotoxicity_to_+34_methylenedioxymethamphetamine__MDMA_:_the_role_of_ambient_temperature_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20634423 DB - PRIME DP - Unbound Medicine ER -