Effects of stress and MDMA on hippocampal gene expression

Georg F. Weber, Bethann N. Johnson, Bryan Yamamoto, Gary A. Gudelsky

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number141396
JournalBioMed Research International
Volume2014
DOIs
StatePublished - 2014
Externally publishedYes

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N-Methyl-3,4-methylenedioxyamphetamine
Gene expression
Gene Expression
Serotonin
Rats
Genes
Rat control
Protein folding
Calcium-Calmodulin-Dependent Protein Kinases
Protein Folding
Street Drugs
Amphetamine
Therapeutics
Circadian Rhythm
Neuropeptides
Transcriptome
Protein Binding
Hippocampus
Carrier Proteins
Down-Regulation

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Effects of stress and MDMA on hippocampal gene expression. / Weber, Georg F.; Johnson, Bethann N.; Yamamoto, Bryan; Gudelsky, Gary A.

In: BioMed Research International, Vol. 2014, 141396, 2014.

Research output: Contribution to journalArticle

Weber, Georg F. ; Johnson, Bethann N. ; Yamamoto, Bryan ; Gudelsky, Gary A. / Effects of stress and MDMA on hippocampal gene expression. In: BioMed Research International. 2014 ; Vol. 2014.
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