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
| Autor: | Sanzio Candeletti, Martina Palmisano, Patrizia Romualdi, Lucia Carboni, Francesca Felicia Caputi |
|---|---|
| Přispěvatelé: | Caputi, F.F, Palmisano, M, Carboni, L, Candeletti, S, Romualdi, P |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine MDMA N-Methyl-3 4-methylenedioxyamphetamine NOP Dynorphin Pharmacology Nucleus accumbens CREB Dynorphins Nucleus Accumbens Rats Sprague-Dawley 03 medical and health sciences Opioid system Serotonin Agents 0302 clinical medicine mental disorders medicine Animals Promoter Regions Genetic Adrenergic Uptake Inhibitors biology Chemistry Nociceptin Dopaminergic Epigenetic Methamphetamine Histone Code Nociceptin receptor 030104 developmental biology Gene Expression Regulation Opioid Peptides biology.protein Histone modification Locomotion 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pharmacological Research. 114:209-218 |
| ISSN: | 1043-6618 |
| DOI: | 10.1016/j.phrs.2016.10.023 |
| Popis: | 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 (8 mg/kg) or repeated (8 mg/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. |
| Databáze: | OpenAIRE |
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