Opioid gene expression changes and post-translational histone modifications at promoter regions in the rat nucleus accumbens after acute and repeated 3,4-methylenedioxy-methamphetamine (MDMA) exposure.
Francesca Felicia Caputi, Martina Palmisano, Lucia Carboni, Sanzio Candeletti, Patrizia Romualdi
Pharmacological Research December 2016 DOI: 10.1016/j.phrs.2016.10.023 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | MDMA |
| Dose | 8 mg/kg (acute); 8 mg/kg twice daily for seven days (repeated) |
| Duration | Seven days of repeated treatment; acute single exposure |
| Topics | MDMA |
| Keywords | Dynorphin Epigenetics Histone modification Nociceptin Opioid system |
| Key findings | MDMA exposure down-regulated the N/OFQ system and up-regulated the DYN system in the nucleus accumbens, with corresponding histone mark changes at their gene promoters. The authors argue that activation of the DYNergic stress system and inactivation of the N/OFQergic anti-stress system contribute to MDMA's neuroadaptive effects and provide epigenetic information related to MDMA abuse. |
Abstract
The recreational drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has been shown to produce neurotoxic damage and long-lasting changes in several brain areas. In addition to the involvement of serotoninergic and dopaminergic systems, little information exists about the contribution of nociceptin/orphaninFQ (N/OFQ)-NOP and dynorphin (DYN)-KOP systems in neuronal adaptations evoked by MDMA. Here we investigated the behavioral and molecular effects induced by acute (8mg/kg) or repeated (8mg/kg twice daily for seven days) MDMA exposure. MDMA exposure affected body weight gain and induced hyperlocomotion; this latter effect progressively decreased after repeated administration. Gene expression analysis indicated a down-regulation of the N/OFQ system and an up-regulation of the DYN system in the nucleus accumbens (NAc), highlighting an opposite systems regulation in response to MDMA exposure. Since histone modifications have been strongly associated to the addiction-related maladaptive changes, we examined two permissive (acH3K9 and me3H3K4) and two repressive transcription marks (me3H3K27 and me2H3K9) at the pertinent opioid gene promoter regions. Chromatin immunoprecipitation assays revealed that acute MDMA increased me3H3K4 at the pN/OFQ, pDYN and NOP promoters. Following acute and repeated treatment a significant decrease of acH3K9 at the pN/OFQ promoter was observed, which correlated with gene expression results. Acute treatment caused an acH3K9 increase and a me2H3K9 decrease at the pDYN promoter which matched its mRNA up-regulation. Our data indicate that the activation of the DYNergic stress system together with the inactivation of the N/OFQergic anti-stress system contribute to the neuroadaptive actions of MDMA and offer novel epigenetic information associated with MDMA abuse.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 5
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- Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies. Journal of Neural Transmission May 1, 2024
- Transcriptomic Analysis of Glycosylation and Neuroregulatory Pathways in Rodent Models in Response to Psychedelic Molecules International Journal of Molecular Sciences January 7, 2023
- MDMA administration reduces ethanol drinking and is associated with altered nociceptin and dynorphin system gene expression in alcohol-preferring rats. Neuropharmacology September 11, 2026
- Activation of Antioxidant and Proteolytic Pathways in the Nigrostriatal Dopaminergic System After 3,4-Methylenedioxymethamphetamine Administration: Sex-Related Differences Frontiers in Pharmacology August 27, 2021
Cites 18
- MDMA enhances emotional empathy and prosocial behavior Social Cognitive and Affective Neuroscience October 4, 2013
- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- Human Pharmacology of 3,4-Methylenedioxymeth-amphetamine ("Ecstasy"): Psychomotor Performance and Subjective Effects Journal of Clinical Psychopharmacology August 1, 2000
- How MDMA's Pharmacology and Pharmacokinetics Drive Desired Effects and Harms The Journal of Clinical Pharmacology January 16, 2014
- Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA Behavioural Pharmacology May 14, 2015
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