title: Effects of stress and MDMA on hippocampal gene expression.
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.
authors: James Winkle College of Pharmacy, University of Cincinnati, 3225 Eden Avenue, Cincinnati, OH 45267, USA.
authors: Georg F
authors: GF
authors: Weber
authors: Department of Neurosciences, University of Toledo School of Medicine, Toledo, OH 43606, USA.
authors: Bethann N
authors: BN
authors: Johnson
authors: Department of Neurosciences, University of Toledo School of Medicine, Toledo, OH 43606, USA.
authors: Bryan K
authors: BK
authors: Yamamoto
authors: James Winkle College of Pharmacy, University of Cincinnati, 3225 Eden Avenue, Cincinnati, OH 45267, USA.
authors: Gary A
authors: GA
authors: Gudelsky
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000235:genetics* / Q000473:pathology; D014176:Protein Biosynthesis; D017510:Protein Folding / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D018490:Serotonin Agents / Q000008:administration & dosage / Q000009:adverse effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D018490:Serotonin Agents; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine