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The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Effects of stress and MDMA on hippocampal gene expression
Georg F Weber1, Bethann N Johnson2, Bryan K Yamamoto2
1James Winkle College of Pharmacy, University of Cincinnati, 3225 Eden Avenue, Cincinnati, OH 45267, USA.
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.
Insights
MDMA (3,4-methylenedioxymethamphetamine) alters gene expression in the hippocampus, impacting neuronal function. Chronic stress modifies these MDMA-induced transcriptional responses, affecting sensory processing and circadian rhythms.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- 3,4-methylenedioxymethamphetamine (MDMA) is a popular drug of abuse with mood-enhancing effects, potentially used under stress.
- Clinical studies suggest MDMA may alleviate symptoms of stress disorders like PTSD.
- Repeated MDMA use can cause persistent deficits in serotonergic (5-HT) nerve terminals, indicating neurotoxicity, which chronic stress may exacerbate.
Purpose of the Study:
- To investigate the transcriptional responses in the hippocampus to MDMA treatment in both control and chronically stressed rats.
- To understand how chronic stress alters the gene expression profile following MDMA administration.
- To examine the impact of MDMA on stress-induced transcriptional changes.
Main Methods:
- Transcriptional profiling of hippocampal tissue from control and chronically stressed rats treated with MDMA.
- Analysis of gene expression changes related to specific cellular processes.
Main Results:
- MDMA altered gene expression involved in protein folding, calmodulin-dependent protein kinase activity, and neuropeptide signaling.
- In stressed rats, MDMA modulated gene expression related to sensory processing and nerve sheath tissue damage.
- MDMA treatment reversed stress-induced downregulation of circadian rhythm genes.
Conclusions:
- MDMA-induced transcriptional responses are associated with persistent effects on neuronal structure and function.
- MDMA treatment modifies the transcriptional signature induced by chronic stress, highlighting complex neurobiological interactions.
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