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The oxytocin analogue carbetocin prevents priming-induced reinstatement of morphine-seeking: Involvement of dopaminergic, noradrenergic and MOPr systems.

Georgiou, P; Zanos, P; Garcia-Carmona, JA; Hourani, S; Kitchen, I; Kieffer, BL; Laorden, ML; Bailey, A (2015) The oxytocin analogue carbetocin prevents priming-induced reinstatement of morphine-seeking: Involvement of dopaminergic, noradrenergic and MOPr systems. European Neuropsychopharmacoly, 25 (12). pp. 2459-2464. ISSN 1873-7862
SGUL Authors: Bailey, Alexis

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Relapse to illicit drug-seeking following abstinence is a major challenge for the treatment of addiction as no effective pharmacotherapy is available. We have recently shown that activating the central oxytocinergic system prevents emotional impairment and stress-induced reinstatement associated with opioid withdrawal. Here, we investigated whether the oxytocin analogue carbetocin (CBT) is able to reverse morphine-primed reinstatement of conditioned-place preference (CPP) in mice. The mechanism underlining the behavioural effect of CBT was investigated by assessing the involvement of the striatal noradrenergic and dopaminergic systems in CBT reversal of priming- and stress-induced reinstatement of opioid CPP. In addition, given recent evidence suggesting the presence of oxytocin receptor (OTR)-μ-opioid receptor (MOPr) interactions in the brain, we further explored these interactions by carrying out OTR autoradiographic binding in brain of mice lacking MOPr. CBT administration prevented priming-induced reinstatement of morphine CPP. While an acute effect of CBT in enhancing dopamine turnover was observed following stress- and priming-induced reinstatement, CBT significantly decreased striatal noradrenaline turnover only following priming-induced reinstatement. Moreover, a significant brain region- specific increase in OTR binding was observed in MOPr knockout mice, indicating the presence of a possible OTR-MOPr interaction, which may be involved in the modulation of relapse. These results support the oxytocinergic system as a promising target for the prevention of relapse to opioid use and highlight the differential involvement of monoaminergic systems on the effects of OTR stimulation in preventing stress- and priming-induced reinstatement of opioid CPP behaviour.

Item Type: Article
Additional Information: © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Keywords: Dopamine, MOPr, Morphine, Noradrenaline, Oxytocin, Reinstatement, 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: European Neuropsychopharmacoly
ISSN: 1873-7862
Language: eng
1 December 2015Published
9 October 2015Published Online
24 September 2015Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Project IDFunderFunder ID
RG120556Royal Society
PubMed ID: 26475574
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