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The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice.

Zanos, P; Georgiou, P; Wright, SR; Hourani, SM; Kitchen, I; Winsky-Sommerer, R; Bailey, A (2014) The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice. Neuropsychopharmacology, 39 (4). pp. 855-865. ISSN 1740-634X https://doi.org/10.1038/npp.2013.285
SGUL Authors: Bailey, Alexis

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Abstract

The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse.

Item Type: Article
Additional Information: © 2014 American College of Neuropsychopharmacology
Keywords: Affective Symptoms, Analysis of Variance, Animals, Brain, Corticosterone, Dose-Response Relationship, Drug, Drug-Seeking Behavior, Male, Mice, Mice, Inbred C57BL, Morphine, Morphine Dependence, Oxytocin, Reinforcement (Psychology), Stress, Psychological, Substance Withdrawal Syndrome, Time Factors, Brain, Animals, Mice, Inbred C57BL, Mice, Morphine Dependence, Substance Withdrawal Syndrome, Morphine, Corticosterone, Oxytocin, Analysis of Variance, Affective Symptoms, Stress, Psychological, Reinforcement (Psychology), Dose-Response Relationship, Drug, Time Factors, Male, Drug-Seeking Behavior, opioid, oxytocin, abstinence, relapse, depression, sociability, Psychiatry, 11 Medical And Health Sciences, 17 Psychology And Cognitive Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Neuropsychopharmacology
ISSN: 1740-634X
Language: eng
Dates:
DateEvent
1 March 2014Published
4 December 2013Published Online
3 October 2013Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
RG120556Royal Societyhttp://dx.doi.org/10.13039/501100000288
PubMed ID: 24129263
Web of Science ID: WOS:000331345300009
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108000
Publisher's version: https://doi.org/10.1038/npp.2013.285

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