NOP Receptor Agonist Ro 64-6198 Decreases Escalation of Cocaine Self-Administration in Rats Genetically Selected for Alcohol Preference

Li, Hongwu; Scuppa, Giulia; Shen, Qianwei; Masi, Alessio; Nasuti, Cinzia; Cannella, Nazzareno; Ciccocioppo, Roberto

doi:10.3389/fpsyt.2019.00176

Cited by 8 publications

(4 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data on alcohol self-administration were recently paralleled in cocaine. We demonstrated that the NOP agonist Ro64-6198 reduced escalated cocaine self-administration in msP but not in Wistar rats [ 195 ], while Cippitelli and colleagues demonstrated that another NOP agonist, AT-312, decreased escalated cocaine self-administration and cocaine hedonic set point in Sprague Dawley rats [ 196 ].…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…These data suggest that the efficacy of AT‐312 in altering cocaine self‐administration is a function of NOP affinity and potency of AT‐312, compared with that of AT‐202, rather than a function of its selectivity. This hypothesis is supported by a recent study in a rat line with upregulated NOP receptor expression, where NOP receptor activation attenuates cocaine self‐administration 42 . To rule out a possible contribution by mu activation in eliciting the observed reduction of cocaine taking, and confirm that it is due to activation of NOP receptors, AT‐312 was administered following treatment with the NOP receptor antagonist SB‐612111.…”

Section: Discussionmentioning

confidence: 65%

Potent and selective NOP receptor activation reduces cocaine self‐administration in rats by lowering hedonic set point

et al. 2019

View full text Add to dashboard Cite

Developing new medications for the treatment of cocaine dependence continues to be a research priority. Compelling evidence indicates that mixed opioid receptor agonists, particularly bifunctional compounds that target nociceptin/orphanin FQ peptide (NOP) and mu opioid receptors, may be useful for the treatment of cocaine addiction. Here, we verify that potent and selective pharmacological activation of NOP receptors is sufficient to reduce relevant facets of cocaine addiction in animal models. Accordingly, we determined whether systemic injections of the small molecule AT-312 (0, 1, 3 mg/kg) could reduce operant cocaine self-administration, motivation for cocaine, and vulnerability to cocaine relapse in rats. Results indicate that a potent and selective NOP receptor agonist was equally efficacious in reducing the number of cocaine infusions in short (1-hour), as well as long (6-hour) access sessions. When tested on an economic-demand reinforcement schedule, AT-312 reduced Q 0 , the parameter that describes the amount of drug consumed at zero price, while leaving the parameter α, a measure of motivation for drug consumption, unaltered. Furthermore, AT-312 successfully reduced conditioned reinstatement of cocaine seeking. In contrast, the NOP receptor agonist did not modify food self-administration. Blockade of the NOP receptor with the antagonist SB-612111 prevented the effect of AT-312 in decreasing cocaine-reinforced responding under a 2-hour fixed ratio 1 schedule, suggesting a NOP receptormediated mechanism. This work demonstrates that potent and selective activation of NOP receptors is sufficient to decrease cocaine taking and seeking behaviors in rats.

show abstract

“…The drug addiction mechanisms are complex and include desire, withdrawal, and relapse. Further studies are needed to verify how NOP agonists can attenuate drug addiction and induce depression (Li et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Behavioral and neurochemical effects of nociceptin/orphanin FQ receptor activation in the social defeat protocol.

Câmara¹,

Brandão

2023

Behavioral Neuroscience

View full text Add to dashboard Cite

The nociceptin/orphanin FQ receptor (NOP receptor) has wide expression in the nervous system and is involved in neurotransmitter release. However, the role of the NOPR in depression is not widely recognized. This study aims to evaluate behavioral and biochemical effects of the NOPR agonist Ro 65-6570 in mice submitted to social defeat protocol. The open-field test, social interaction test, and tail suspension test were applied to evaluate depressive behavior in male Swiss mice. Blood and brain tissue samples were obtained to evaluate the oxidative stress. The NOP agonist, Ro 65-6570 (1 mg/kg), or the social defeat stress reduced exploration rate in the open-field test. The social defeat stress and/or the NOP agonist also increased immobility time in the tail suspension test and the grooming time, as well as reduced the social interaction on the last day of social defeat protocol. Seven days after the end of the protocol, only the drug alone was able to affect the animals' interaction. Additionally, the NOP agonist increased the concentration of carbonyl groups (CGs) in hippocampus and malondialdehyde in serum. The stress of social defeat and the NOP agonist, together, increased malondialdehyde in animals' serum and prefrontal cortex, as well as increased the CGs concentration in the prefrontal cortex. These findings indicate a chronic depressive effect induced by the NOPR activation, sometimes regardless of the social defeat stress. We suggest that the NOPR signaling can activate pathways involved in cellular oxidative stress, contributing to the depression pathology.

show abstract

NOP Receptor Agonist Ro 64-6198 Decreases Escalation of Cocaine Self-Administration in Rats Genetically Selected for Alcohol Preference

Cited by 8 publications

References 54 publications

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

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

Potent and selective NOP receptor activation reduces cocaine self‐administration in rats by lowering hedonic set point

Behavioral and neurochemical effects of nociceptin/orphanin FQ receptor activation in the social defeat protocol.

Contact Info

Product

Resources

About