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

Georgiou, Polymnia; Zanos, Panos; García-Carmona, Juan Antonio; Hourani, S.M.O.; Kitchen, Ian; Kieffer, Brigitte L.; Laorden, María‐Luisa; Bailey, Alexis

doi:10.1016/j.euroneuro.2015.09.015

Cited by 45 publications

(34 citation statements)

References 17 publications

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“…Furthermore, no studies have been published showing that oxytocin impacts heroin reinstatement. Related, carbetocin, an oxytocin analogue, reduced stress-induced (Zanos et al, 2014) and drug-primed (Georgiou et al, 2015) reinstatement of morphine-seeking. Preliminary data from our laboratory (Fig.…”

Section: Oxytocin Effects On Preclinical Models Of Addictionmentioning

confidence: 99%

Oxytocin and Rodent Models of Addiction

Leong

Cox

King

et al. 2018

International Review of Neurobiology

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Interest for the use of oxytocin as a treatment for addiction began over 40years ago. Better known for its roles in parturition, lactation and pair bonding, oxytocin also has anxiolytic properties, reduces immune and inflammatory responses, and has a role in learning and memory. In this chapter, oxytocin effects on addiction processes are described by highlighting research findings that have used oxytocin within current preclinical animal models of addiction, relapse, or craving. First, we provide a brief background of the endogenous oxytocin system followed by descriptions of the behavioral models used to study addiction, including models of drug taking and seeking. Then we review recent preclinical studies that have used oxytocin as a therapeutic intervention throughout multiple stages of the addiction cycle from a behavioral and neurobiological perspective. These models encompass the entire range of the addiction cycle including acquisition and maintenance of drug taking, withdrawal and craving during periods of drug abstinence, and ultimately relapse. We then posit several theories about how oxytocin interacts with both drug and social reward, as well as presenting a mechanistic account of how specific oxytocin receptor localization may contribute to oxytocin's efficacy as an addiction therapeutic.

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Section: Oxytocin Effects On Preclinical Models Of Addictionmentioning

confidence: 99%

Oxytocin and Rodent Models of Addiction

Leong

Cox

King

et al. 2018

International Review of Neurobiology

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“…Trunk blood from saline-and METH-treated/withdrawn mice was collected in EDTA-containing tubes and spun for 15 min at 2000 x g at 4 o C. Plasma was collected and corticosterone levels were measured using a rat/mouse corticosterone [ 125 I] kit (MP Biomedicals, USA), according to the manufacturer's instructions; also see Georgiou et al (2015b).…”

Section: Plasma Corticosterone Levels (Experiments 3)mentioning

confidence: 99%

Methamphetamine abstinence induces changes in μ-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype

et al. 2016

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Methamphetamine abstinence induces changes in μ-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype, Neuropharmacology (2016), doi: 10.1016/ j.neuropharm.2016.02.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Similarly, in humans, carbetocin had a prolonged effect on post‐partum uterine activity in terms of both a higher amplitude and frequency of contractions compared to oxytocin . Concerning the central effects of carbetocin, studies in rodents demonstrated that carbetocin reduced anxiety‐like behaviours in the elevated plus maze test , had antidepressant‐like effects in the forced swimming test and attenuated the negative emotional consequences of opioid withdrawal .…”

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confidence: 99%

Carbetocin is a Functional Selective Gq Agonist That Does Not Promote Oxytocin Receptor Recycling After Inducing β‐Arrestin‐Independent Internalisation

Passoni

Leonzino

Gigliucci

et al. 2016

J Neuroendocrinology

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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Carbetocin, a long-acting oxytocin analogue, has been reported to elicit interesting and peculiar behavioural effects. The present study investigated the molecular pharmacology of carbetocin, aiming to better understand the molecular basis of its action in the brain. Using bioluminescence resonance energy transfer biosensors, we characterised the effects of carbetocin on the three human oxytocin/vasopressin receptors expressed in the nervous system: the oxytocin receptor (OXTR) and the vasopressin V1a (V1aR) and V1b (V1bR) receptors. Our results indicate that (i) carbetocin activates the OXTR but not the V1aR and V1bR at which it may act as an antagonist; (ii) carbetocin selectively activates only the OXTR/Gq pathway displaying a strong functional selectivity; (iii) carbetocin is a partial agonist at the OXTR/Gq coupling; (iv) carbetocin promotes OXTR internalisation via a previously unreported b-arrestin-independent pathway; and (v) carbetocin does not induce OXTR recycling to the plasma membrane. Altogether, these molecular pharmacology features identify carbetocin as a substantially different analogue compared to the endogenous oxytocin and, consequently, carbetocin is not expected to mimic oxytocin in the brain. Whether these unique features of carbetocin could be exploited therapeutically remains to be established. Oxytocin is a small nonapeptide produced by magnocellular and parvocellular neurones of the supraoptic and paraventricular nuclei of the hypothalamus; from these sites of synthesis, the peptide is delivered to the periphery by axons projecting to the posterior pituitary and to the central nervous system (CNS) by dendrites and axonal collaterals (1,2). In the periphery, oxytocin has several functions, including the contraction of uterine smooth muscles during labour, an effect that has been extensively exploited for decades to promote contractions during the third stage of labour and to control bleeding after childbirth (3,4). Oxytocin also promotes the contraction of the mammary myoepithelium during lactation (5) and the intranasal use of oxytocin to stimulate lactation in breastfeeding women was approved by the Food and Drug Administration in the USA in 1960, even though it was discontinued in 1997 for commercial reasons.In the CNS, oxytocin acts as a neurotransmitter/neuromodulator regulating several aspects of social behaviour, learning and memory processes, and stress and anxiety responses (6,7). On the basis of its capability to promote social interactions in all vertebrates, including humans, oxytocin has been proposed as a clinical treatment for relieving social impairments associated with neurodevelopmental and psychiatric disorders (8,9). In the past decade, a number of clinical trials have been performed in autism and schizophrenia but, unfortunately, no consensus on the real efficacy of o...

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

Cited by 45 publications

References 17 publications

Oxytocin and Rodent Models of Addiction

Oxytocin and Rodent Models of Addiction

Methamphetamine abstinence induces changes in μ-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype

Carbetocin is a Functional Selective Gq Agonist That Does Not Promote Oxytocin Receptor Recycling After Inducing β‐Arrestin‐Independent Internalisation

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