Low-dose Nociceptin/Orphanin FQ reduces anxiety-like performance in alcohol-withdrawn, but not alcohol-naïve, Male Wistar rats

Aujla, Harinder; Nedjadrasul, Daniel

doi:10.1016/j.neuropharm.2015.01.006

Cited by 6 publications

(3 citation statements)

References 42 publications

(56 reference statements)

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“…Interestingly, OFQ/N has been found to exert greater anxiolytic effects in animals with prior alcohol experience compared to their alcohol-naive controls. 201 However, in the same study, OFQ/N failed to reduce anxiety in alcohol-naive rats. 201 Thus, further studies are needed to determine if OFQ/N would exert an anxiolytic effect in subjects with prior cocaine experience.…”

Section: Molecular Mechanisms Of Cocaine Addictionmentioning

confidence: 86%

“…201 However, in the same study, OFQ/N failed to reduce anxiety in alcohol-naive rats. 201 Thus, further studies are needed to determine if OFQ/N would exert an anxiolytic effect in subjects with prior cocaine experience. This is particularly important because there are some reports showing that OFQ/N could be anxiogenic under certain experimental conditions.…”

Section: Molecular Mechanisms Of Cocaine Addictionmentioning

confidence: 86%

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The Nociceptin Receptor as an Emerging Molecular Target for Cocaine Addiction

Lutfy

Zaveri

2016

Progress in Molecular Biology and Translational Science

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Cocaine addiction is a global public health and socioeconomic issue that requires pharmacological and cognitive therapies. Currently there are no FDA-approved medications to treat cocaine addiction. However, in preclinical studies, interventions ranging from herbal medicine to deep-brain stimulation have shown promise for the therapy of cocaine addiction. Recent developments in molecular biology, pharmacology, and medicinal chemistry have enabled scientists to identify novel molecular targets along the pathways involved in drug addiction. In 1994, a receptor that showed a great deal of homology to the traditional opioid receptors was characterized. However, endogenous and exogenous opioids failed to bind to this receptor, which led scientists to name it opioid receptor-like receptor, now referred to as the nociceptin receptor. The endogenous ligand of NOPr was identified a year later and named orphanin FQ/nociceptin. Nociceptin and NOPr are widely distributed through-out the CNS and are involved in many physiological responses, such as food intake, nociceptive processing, neurotransmitter release, etc. Furthermore, exogenous nociceptin has been shown to regulate the activity of mesolimbic dopaminergic neurons, glutamate, and opioid systems, and the stress circuit. Importantly, exogenous nociceptin has been shown to reduce the rewarding and addictive actions of a number of drugs of abuse, such as psychostimulants, alcohol, and opioids. This paper reviews the existing literature on the role of endogenous nociceptin in the rewarding and addictive actions of cocaine. The effect of exogenous nociceptin on these processes is also reviewed. Furthermore, the effects of novel small-molecule NOPr ligands on these actions of cocaine are discussed. Overall, a review of the literature suggests that NOPr could be an emerging target for cocaine addiction pharmacotherapy.

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Section: Molecular Mechanisms Of Cocaine Addictionmentioning

confidence: 86%

Section: Molecular Mechanisms Of Cocaine Addictionmentioning

confidence: 86%

The Nociceptin Receptor as an Emerging Molecular Target for Cocaine Addiction

Lutfy

Zaveri

2016

Progress in Molecular Biology and Translational Science

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“…Confirming a pivotal role of N/OFQ in mediating the interaction between stress and alcohol in the CeA, N/OFQ was shown to revert CRF-enhanced GABA-mediated inhibitory post-synaptic potentials (IPSPs) in CeA slices of both naïve and ethanol-intoxicated rats [ 101 ]. N/OFQ also attenuated the expression of psychological and physical signs of alcohol withdrawal [ 190 , 191 ], a phenomenon leading to binge intoxication mediated by neurocircuitries pivoted in the CeA (for review see [ 192 ]). In line with exogenous delivery of the neuropeptide, peripheral administration of the NOP agonist MT-7716 reduced alcohol intake in msP rats over two weeks of treatment without sign of tolerance and the effect persisted for one additional week after treatment discontinuation [ 193 ].…”

Section: Role Of N/ofq-nop Receptor System In the Interaction Between Stress And Drug Addictionmentioning

confidence: 99%

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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