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Chronic unpredictable stress augments +3,4-methylenedioxymethamphetamine-induced monoamine depletions: the role of corticosterone.
Neuroscience. 2009 Apr 10; 159(4):1233-43.N

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.

Authors+Show Affiliations

Department of Pharmacology and Experimental Therapeutics, Laboratory of Neurochemistry, Boston University School of Medicine, Boston, MA 02118, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19409219

Citation

Johnson, B N., and B K. Yamamoto. "Chronic Unpredictable Stress Augments +3,4-methylenedioxymethamphetamine-induced Monoamine Depletions: the Role of Corticosterone." Neuroscience, vol. 159, no. 4, 2009, pp. 1233-43.
Johnson BN, Yamamoto BK. Chronic unpredictable stress augments +3,4-methylenedioxymethamphetamine-induced monoamine depletions: the role of corticosterone. Neuroscience. 2009;159(4):1233-43.
Johnson, B. N., & Yamamoto, B. K. (2009). Chronic unpredictable stress augments +3,4-methylenedioxymethamphetamine-induced monoamine depletions: the role of corticosterone. Neuroscience, 159(4), 1233-43. https://doi.org/10.1016/j.neuroscience.2009.01.067
Johnson BN, Yamamoto BK. Chronic Unpredictable Stress Augments +3,4-methylenedioxymethamphetamine-induced Monoamine Depletions: the Role of Corticosterone. Neuroscience. 2009 Apr 10;159(4):1233-43. PubMed PMID: 19409219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic unpredictable stress augments +3,4-methylenedioxymethamphetamine-induced monoamine depletions: the role of corticosterone. AU - Johnson,B N, AU - Yamamoto,B K, Y1 - 2009/02/03/ PY - 2008/10/30/received PY - 2009/01/14/revised PY - 2009/01/29/accepted PY - 2009/5/5/entrez PY - 2009/5/5/pubmed PY - 2009/8/21/medline SP - 1233 EP - 43 JF - Neuroscience JO - Neuroscience VL - 159 IS - 4 N2 - 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. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/19409219/Chronic_unpredictable_stress_augments_+34_methylenedioxymethamphetamine_induced_monoamine_depletions:_the_role_of_corticosterone_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(09)00130-4 DB - PRIME DP - Unbound Medicine ER -