Differential modulation of ventral tegmental area circuits by the nociceptin/orphanin FQ system

Driscoll, Joseph R.; Wallace, Tanya L.; Mansourian, Kasra; Martin, William J.; Margolis, Elyssa B.

doi:10.1101/776484

Cited by 2 publications

(1 citation statement)

References 110 publications

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“…However, with regard to this inconsistency, it is important to consider that the VTA contains two populations of NOP positive neurons (Figure 4); the first one co‐express tyrosine hydroxylase and its activation negatively regulates dopamine transmission (Norton et al, 2002; Zheng et al, 2002). The second population is negative to tyrosine hydroxylase and is composed of GABA and glutamate cells that are located presynaptically and, by impinging onto dopamine neurons, regulate the activity of the VTA dopamine system (Driscoll et al, 2020). It is known that N/OFQ acting at presynaptic level inhibits GABA release onto dopamine neurons that may potentially result in their disinhibition (Zheng et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Genetic deletion or pharmacological blockade of nociceptin/orphanin FQ receptors in the ventral tegmental area attenuates nicotine‐motivated behaviour

Domi

Lunerti

Petrella

et al. 2022

British J Pharmacology

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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·kg−1) on nicotine self‐administration. NOP receptor blockade was further evaluated at the brain circuitry level, by microinjecting LY2817412 (3.0 & 6.0 μg·μl−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.

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Section: Discussionmentioning

confidence: 99%

Genetic deletion or pharmacological blockade of nociceptin/orphanin FQ receptors in the ventral tegmental area attenuates nicotine‐motivated behaviour

Domi

Lunerti

Petrella

et al. 2022

British J Pharmacology

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Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

Ubaldi

Cannella

Borruto

et al. 2021

IJMS

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Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

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Differential modulation of ventral tegmental area circuits by the nociceptin/orphanin FQ system

Cited by 2 publications

References 110 publications

Genetic deletion or pharmacological blockade of nociceptin/orphanin FQ receptors in the ventral tegmental area attenuates nicotine‐motivated behaviour

Genetic deletion or pharmacological blockade of nociceptin/orphanin FQ receptors in the ventral tegmental area attenuates nicotine‐motivated behaviour

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

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