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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 and 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.

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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
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Zanos, PUNSPECIFIEDUNSPECIFIED
Georgiou, PUNSPECIFIEDUNSPECIFIED
Wright, SRUNSPECIFIEDUNSPECIFIED
Hourani, SMUNSPECIFIEDUNSPECIFIED
Kitchen, IUNSPECIFIEDUNSPECIFIED
Winsky-Sommerer, RUNSPECIFIEDUNSPECIFIED
Bailey, AUNSPECIFIEDUNSPECIFIED
Date : March 2014
Identification Number : 10.1038/npp.2013.285
Additional Information : This is an electronic version of an article published in Neuropsychopharmacology (2014), DOI: 10.1038/npp.2013.285 Link to the published version: http://dx.doi.org/10.1038/npp.2013.285.
Depositing User : Symplectic Elements
Date Deposited : 04 Nov 2014 10:17
Last Modified : 17 Nov 2014 14:33
URI: http://epubs.surrey.ac.uk/id/eprint/806336

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