Effects of stress and MDMA on hippocampal gene expression.

Publisher: Hindawi Pub. Co Country of Publication: United States NLM ID: 101600173 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE

Original Publication: New York, NY : Hindawi Pub. Co.

Protein Biosynthesis*; 3,4-Methylenedioxyamphetamine/*analogs & derivatives ; Hippocampus/*metabolism ; Neurotoxicity Syndromes/*genetics ; Stress Disorders, Post-Traumatic/*genetics; 3,4-Methylenedioxyamphetamine/administration & dosage ; 3,4-Methylenedioxyamphetamine/adverse effects ; Animals ; Gene Expression Regulation ; Neurotoxicity Syndromes/pathology ; Protein Folding/drug effects ; Rats ; Serotonin/genetics ; Serotonin/metabolism ; Serotonin Agents/administration & dosage ; Serotonin Agents/adverse effects ; Stress Disorders, Post-Traumatic/drug therapy ; Stress Disorders, Post-Traumatic/pathology

MDMA (3,4-methylenedioxymethamphetamine) is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD). On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT) nerve terminals that have been viewed as indicative of 5-HT neurotoxicity. Exposure to chronic stress has been shown to augment MDMA-induced 5-HT neurotoxicity. Here, we examine the transcriptional responses in the hippocampus to MDMA treatment of control rats and rats exposed to chronic stress. MDMA altered the expression of genes that regulate unfolded protein binding, protein folding, calmodulin-dependent protein kinase activity, and neuropeptide signaling. In stressed rats, the gene expression profile in response to MDMA was altered to affect sensory processing and responses to tissue damage in nerve sheaths. Subsequent treatment with MDMA also markedly altered the genetic responses to stress such that the stress-induced downregulation of genes related to the circadian rhythm was reversed. The data support the view that MDMA-induced transcriptional responses accompany the persistent effects of this drug on neuronal structure/function. In addition, MDMA treatment alters the stress-induced transcriptional signature.

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R01 DA007606 United States DA NIDA NIH HHS; USPHS DA047247 United States DA NIDA NIH HHS

0 (Serotonin Agents)
333DO1RDJY (Serotonin)
4764-17-4 (3,4-Methylenedioxyamphetamine)
ML1I4KK67B (3,4-methylenedioxyethamphetamine)

Date Created: 20140211 Date Completed: 20141216 Latest Revision: 20211021

20231215

PMC3910535

10.1155/2014/141396

24511526