title: Cocaine abstinence induces emotional impairment and brain region-specific upregulation of the oxytocin receptor binding.
abstract: The key problem in treating cocaine addiction is the maintenance of a drug-free state as negative emotional symptoms during abstinence often trigger relapse. The mechanisms underpinning the emotional dysregulation during abstinence are currently not well-understood. There is evidence suggesting a role of the neuropeptide oxytocin in the modulation of drug addiction processes. However, its involvement during long-term abstinence from cocaine use remains unclear. In this study, we aimed to behaviourally characterize a mouse model of long-term cocaine withdrawal and assess the effect of chronic cocaine administration and long-term cocaine abstinence on the central oxytocinergic system and the hypothalamic-pituitary-adrenal axis. Fourteen-day escalating-dose cocaine administration (3 × 15-30 mg/kg/day) and 14-day withdrawal increased plasma corticosterone levels and oxytocin receptor (OTR) binding in piriform cortex, lateral septum and amygdala. A specific cocaine withdrawal-induced increase in OTR binding was observed in the medial septum. These biochemical alterations occurred concomitantly with the emergence of memory impairment, contextual psychomotor sensitization and an anhedonic and anxiogenic phenotype during withdrawal. Our study established a clear relationship between cocaine abstinence and emotional impairment in a novel translationally relevant model of cocaine withdrawal and demonstrated for the first time brain region-specific neuroadaptations of the oxytocin system, which may contribute to abstinence-induced negative emotional state.
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.|Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Polymnia
authors.initials: P
authors.lastname: Georgiou
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.|Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Panos
authors.initials: P
authors.lastname: Zanos
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.
authors.forename: Susanna
authors.initials: S
authors.lastname: Hourani
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Kitchen
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK. abailey@sgul.ac.uk.|Institute of Medical and Biomedical Education, St George's University of London, London, SW17 0R, UK. abailey@sgul.ac.uk.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004644:Emotions / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D018045:Receptors, Oxytocin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018045:Receptors, Oxytocin; D003042:Cocaine; D003345:Corticosterone
keywords: anhedonia; anxiety; cocaine withdrawal; corticosterone; mice