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Genetic deletion or pharmacological blockade of nociceptin/orphanin FQ receptors in the ventral tegmental area attenuates nicotine-motivated behaviour
Univ Camerino, Italy.
Univ Camerino, Italy.
Univ Camerino, Italy.
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-5726-4814
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2022 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 179, no 11, p. 2647-2658Article in journal (Refereed) Published
Abstract [en]

Background and Purpose The nociceptin/orphanin FQ (N/OFQ)-nociceptin opioid-like peptide (NOP) receptor system is widely distributed in the brain and pharmacological activation of this system revealed therapeutic potential in animal models of substance use disorder. Studies also showed that genetic deletion or pharmacological blockade of NOP receptors confer resistance to the development of alcohol abuse. Here, we have used a genetic and pharmacological approach to evaluate the therapeutic potential of NOP antagonism in smoking cessation. Experimental Approach Constitutive NOP receptor knockout rats (NOP-/-) and their wild-type counterparts (NOP+/+) were tested over a range of behaviours to characterize their motivation for nicotine. We next explored the effects of systemic administration of the NOP receptor antagonist LY2817412 (1.0 & 3.0 mg center dot kg(-1)) on nicotine self-administration. NOP receptor blockade was further evaluated at the brain circuitry level, by microinjecting LY2817412 (3.0 & 6.0 mu g center dot mu l(-1)) into the ventral tegmental area (VTA), nucleus accumbens (NAc) and central amygdala (CeA). Key Results Genetic NOP receptor deletion resulted in decreased nicotine intake, decreased motivation to self-administer and attenuation of cue-induced nicotine reinstatement. LY2817412 reduced nicotine intake in NOP+/+ but not in NOP-/- rats, confirming that its effect is mediated by inhibition of NOP transmission. Finally, injection of LY2817412 into the VTA but not into the NAc or CeA decreased nicotine self-administration. Conclusions and Implications These findings indicate that inhibition of NOP transmission attenuates the motivation for nicotine through mechanisms involving the VTA and suggest that NOP receptor antagonism may represent a potential treatment for smoking cessation.

Place, publisher, year, edition, pages
WILEY , 2022. Vol. 179, no 11, p. 2647-2658
Keywords [en]
nicotine; NOP; reinforcement; relapse; reward; VTA
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-183228DOI: 10.1111/bph.15762ISI: 000753476300001PubMedID: 34854073OAI: oai:DiVA.org:liu-183228DiVA, id: diva2:1641364
Note

Funding Agencies|National Institute on Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA014351, PRIN 2017SXEXT5]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA

Available from: 2022-03-01 Created: 2022-03-01 Last updated: 2023-02-16Bibliographically approved

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Domi, Esi

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