Chronic unpredictable stress augments +3,4-methylenedioxymethamphetamine-induced monoamine depletions: the role of corticosterone.
B N Johnson, Bryan K. Yamamoto
Neuroscience April 10, 2009 DOI: 10.1016/j.neuroscience.2009.01.067 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA Chronic unpredictable stress Metyrapone |
| Dose | MDMA 5 mg/kg every 2 h (four doses); metyrapone 50 mg/kg i.p. |
| Duration | 10 days of stress, MDMA challenge on day 11, rats killed 5 days later |
| Topics | MDMA |
| Key findings | Chronic unpredictable stress enhanced MDMA-induced serotonin depletions in all three brain regions and produced striatal dopamine depletion only in stressed rats; these effects were blocked by the corticosterone synthesis inhibitor metyrapone, suggesting a role for elevated basal corticosterone. |
Abstract
Exposure to stress alters the behavioral and neurochemical effects of drugs of abuse. However, it is unknown if chronic stress can affect the serotonergic depletions induced by the psychostimulant drug 3,4-methylenedioxymethamphetamine (MDMA). Rats were exposed to 10 days of chronic unpredictable stress (CUS) which resulted in the predicted elevation of basal plasma corticosterone concentrations. On the 11th day, rats received four challenge doses of MDMA (5 mg/kg every 2 h, i.p.) or saline. Five days later, rats were killed and serotonin (5-HT) and dopamine content were measured in the striatum, hippocampus, and frontal cortex. MDMA produced greater depletions of 5-HT in all three brain regions of rats pre-exposed to CUS compared to rats not exposed to CUS. CUS-exposed rats also had an augmented acute hyperthermic response but a similar increase in plasma corticosterone after challenge injections of MDMA compared with non-stressed rats similarly challenged with MDMA. Moreover, CUS-exposed rats exhibited an MDMA-induced depletion of striatal dopamine that was absent in non-stressed rats that received MDMA. To investigate the role of corticosterone in these effects, the corticosterone synthesis inhibitor, metyrapone (50 mg/kg i.p.), was administered prior to each stressor on each of the 10 days of CUS. Metyrapone blocked the chronic stress-induced elevation in basal plasma corticosterone, prevented the enhancement of MDMA-induced hyperthermia, and blocked the enhanced depletions of 5-HT and dopamine in CUS-exposed rats, but had no effect on the acute MDMA-induced increases in plasma corticosterone. These findings suggest that CUS alone can increase the basal level of corticosterone that in turn, plays an important role in enhancing the sensitivity of both 5-HT and dopamine terminals to the hyperthermic and monoamine depleting effects of MDMA without altering the acute corticosterone response to an MDMA challenge.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 7
- Chronic Stress Enhances the Corticosterone Response and Neurotoxicity to +3,4-Methylenedioxymethamphetamine (MDMA): The Role of Ambient Temperature Journal of Pharmacology and Experimental Therapeutics July 16, 2010
- Effects of Stress and MDMA on Hippocampal Gene Expression BioMed Research International 2014
- Age differences in (±) 3,4‐methylenedioxymethamphetamine (MDMA)‐induced conditioned taste aversions and monoaminergic levels Developmental Psychobiology June 15, 2013
- Differential role of dose and environment in initiating and intensifying neurotoxicity caused by MDMA in rats BMC Pharmacology and Toxicology August 5, 2019
- Cognitive and behavioural effects induced by social stress plus MDMA administration in mice. Behavioural Brain Research February 15, 2017
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Cites 13
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- 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, “Ecstasy”): pharmacology and toxicology in animals and humans Addiction May 1, 1994
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
and 8 more in the library