title: Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence.
abstract: Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals.
authors.affiliation: Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U 964, CNRS UMR 7104, Université de Strasbourg, France.|Département de Psychiatrie I, Hôpital Civil, Centre Hospitalier Régional Universitaire de Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Lalanne
authors.affiliation: Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U 964, CNRS UMR 7104, Université de Strasbourg, France.|Douglas Institute Research Centre, McGill University, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Ayranci
authors.affiliation: Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U 964, CNRS UMR 7104, Université de Strasbourg, France.|Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, Université de Strasbourg, CNRS, Faculté de Psychologie, Neuropôle de Strasbourg, France.
authors.forename: D
authors.initials: D
authors.lastname: Filliol
authors.affiliation: Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U 964, CNRS UMR 7104, Université de Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Gavériaux-Ruff
authors.affiliation: Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U 964, CNRS UMR 7104, Université de Strasbourg, France.|Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, Université de Strasbourg, CNRS, Faculté de Psychologie, Neuropôle de Strasbourg, France.
authors.forename: K
authors.initials: K
authors.lastname: Befort
authors.affiliation: Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U 964, CNRS UMR 7104, Université de Strasbourg, France.|Douglas Institute Research Centre, McGill University, Canada.
authors.forename: B L
authors.initials: BL
authors.lastname: Kieffer
authors.affiliation: Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U 964, CNRS UMR 7104, Université de Strasbourg, France.|McGill Group for Suicide Studies, Douglas Institute Research Centre, McGill University, Canada.
authors.forename: P-E
authors.identifier: http://orcid.org/0000-0003-3383-1604
authors.initials: PE
authors.lastname: Lutz
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000627:therapeutic use; D006120:Grooming / Q000187:drug effects*; D003932:Heroin / Q000494:pharmacology; D006556:Heroin Dependence / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000031:analogs & derivatives / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D012919:Social Behavior; D013995:Time; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D005473:Fluoxetine; C051844:norbinaltorphimine; D009271:Naltrexone; D003932:Heroin
keywords: abstinence; addiction; heroin; kappa opioid receptor; serotonin; sociability