Chronic Stress Enhances the Corticosterone Response and Neurotoxicity to +3,4-Methylenedioxymethamphetamine (MDMA): The Role of Ambient Temperature
Bethann N. Johnson, Bryan K. Yamamoto
Journal of Pharmacology and Experimental Therapeutics July 16, 2010 DOI: 10.1124/jpet.110.171322 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Chronic unpredictable stress MDMA reduced ambient temperature metyrapone |
| Dose | 5 mg/kg i.p. once every 2 h for a total of four injections |
| Duration | 10 days of CUS, followed by MDMA challenge |
| Topics | MDMA Serotonin |
| Keywords | Monoamine neurotransmitter Corticosterone Hyperthermia Neurochemical Endocrinology Dopamine Metyrapone Neurotoxicity Pharmacology Hippocampus |
| Citations | 22 |
| Key findings | Chronic unpredictable stress enhances MDMA-induced hyperthermia and long-term serotonin and dopamine depletions, and this enhancement is mediated by hyperthermia but not by corticosterone. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 5
- Effects of Stress and MDMA on Hippocampal Gene Expression BioMed Research International 2014
- Autophagy inhibition plays a protective role against 3, 4‐methylenedioxymethamphetamine (MDMA)‐induced loss of serotonin transporters and depressive‐like behaviors in rats Pharmacological Research February 28, 2019
- Cognitive and behavioural effects induced by social stress plus MDMA administration in mice. Behavioural Brain Research February 15, 2017
- Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study. European Neuropsychopharmacology January 2016
- "Ecstasy"-induced toxicity in SH-SY5Y differentiated cells: role of hyperthermia and metabolites. Archives of Toxicology February 2014
Cites 9
- Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics July 1, 1999
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Methylenedioxymethamphetamine-induced hyperthermia and neurotoxicity are independently mediated by 5-HT2 receptors Brain Research October 1, 1990
- Cutaneous Vasoconstriction Contributes to Hyperthermia Induced by 3,4-Methylenedioxymethamphetamine (Ecstasy) in Conscious Rabbits Journal of Neuroscience November 1, 2001
and 4 more in the library