Effects of Stress and MDMA on Hippocampal Gene Expression
BioMed Research International – January 01, 2014
Source: OpenAlex
Summary
MDMA significantly influences gene expression related to stress and neuronal function. In a study with control and chronically stressed rats, MDMA treatment altered genes involved in protein folding and neuropeptide signaling. Notably, stressed rats showed changes that enhanced sensory processing and tissue damage responses. Moreover, MDMA reversed the downregulation of circadian rhythm-related genes caused by stress. These findings highlight the complex interplay between MDMA's effects on serotonin neurotoxicity and its potential therapeutic benefits for stress disorders like PTSD, suggesting lasting impacts on brain structure and function.
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.