Distinct Mu, Delta, and Kappa Opioid Receptor Mechanisms Underlie Low Sociability and Depressive-Like Behaviors During Heroin Abstinence
| Autor: | Paul Chu-Sin-Chung, Audrey Matifas, Gulebru Ayranci, Abdel-Mouttalib Ouagazzal, Brigitte L. Kieffer, Pascale Koebel, Dominique Filliol, Katia Befort, Pierre-Eric Lutz |
|---|---|
| Přispěvatelé: | Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Section Neuroscience |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Dorsal Raphe Nucleus
Male Narcotics medicine.medical_specialty Mice 129 Strain media_common.quotation_subject [SDV]Life Sciences [q-bio] Receptors Opioid mu Craving κ-opioid receptor Heroin Fluoxetine mental disorders medicine Animals Social Behavior Psychiatry Spatial Memory media_common Mice Knockout Pharmacology Memory Disorders Depression Heroin Dependence Receptors Opioid kappa Addiction Abstinence Substance Withdrawal Syndrome 3. Good health Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Memory Short-Term Opioid Antidepressive Agents Second-Generation Antidepressant Original Article medicine.symptom Opiate Psychology Neuroscience medicine.drug |
| Zdroj: | Neuropsychopharmacology Neuropsychopharmacology, Nature Publishing Group, 2014, 39 (11), pp.2694-2705. ⟨10.1038/npp.2014.126⟩ |
| ISSN: | 0893-133X 0007-0920 |
| Popis: | International audience; Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse. |
| Databáze: | OpenAIRE |
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