<scp>MT</scp>‐7716, a potent <scp>NOP</scp> receptor agonist, preferentially reduces ethanol seeking and reinforcement in post‐dependent rats

Guglielmo, Giordano de; Martin‐Fardon, Rémi; Teshima, Koji; Ciccocioppo, Roberto; Weiss, Friedbert

doi:10.1111/adb.12157

Cited by 48 publications

(55 citation statements)

References 39 publications

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“…This is consistent with a NOP receptor agonist-induced decrease in extracellular dopamine in the NAc (Murphy et al, 1996;Vazquez-DeRose et al, 2013). Nevertheless, the ability of NOP receptor agonists to block self-administration of these drugs appears to be far less robust, if effective at all (Walker et al, 1998;Ciccocioppo et al, 2014;de Guglielmo et al, 2015). One difference in the way in which NOP receptor agonists have been tested in these two "drug abuse" paradigms is that NOP receptor agonists block acquisition of CPP but generally have been tested for their ability to block expression of selfadministration.…”

Section: Future Directions and New Toolssupporting

confidence: 75%

“…N/OFQ and the selective small molecule agonist Ro 64-6198 have both been demonstrated to block ethanol selfadministration in rats (Ciccocioppo et al, 1999(Ciccocioppo et al, , 2004Kuzmin et al, 2007); however, these studies have been generally conducted in alcohol preferring rat strains, some of which, including the Marchigian Sardinian alcohol preferring rat line, showed anomalies in their NOP-N/OFQ system (Economidou et al, 2008). Other studies found NOP agonists to be effective in decreasing alcohol drinking only in rats with a previous history of alcohol dependence but not in unselected or nondependent rat lines de Guglielmo et al, 2015). A single publication found efficacy in normal Wistar rats (Kuzmin et al, 2007).…”

Section: Biologic Actions Of Nociceptin Opioid Peptide Receptorsmentioning

confidence: 99%

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Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

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The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor

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Section: Future Directions and New Toolssupporting

confidence: 75%

Section: Biologic Actions Of Nociceptin Opioid Peptide Receptorsmentioning

confidence: 99%

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

et al. 2016

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“…These rats showed that NPS specifically exerts anxiolytic effects on msP rats. A similar phenomenon was previously observed for drugs such as nociception agonists and CRF1 receptor antagonists; both classes of compounds possess marked anxiolytic effects and reduced alcohol drinking in msP rats but not in heterogeneous Wistar rats (Ayanwuyi et al 2013; Ciccocioppo et al 2014; de Guglielmo et al 2015; Gehlert et al 2007). Most importantly, our finding agrees with previous studies published in genetically selected alcohol-preferring P rats, in which ICV administration of NPS attenuated home cage alcohol drinking and elicited a marked anxiolytic effect (Badia-Elder et al 2008).…”

Section: Discussionsupporting

confidence: 81%

Neuropeptide S differently modulates alcohol-related behaviors in alcohol-preferring and non-preferring rats

Cannella

Kallupi

et al. 2016

Psychopharmacology

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Rationale Neuropeptide S (NPS) displays unique pharmacological properties and induces both anxiolytic and pro-stress/arousal activities. Previous studies performed using Wistar rats demonstrated that NPS facilitated alcohol and cocaine seeking but did not affect alcohol or cocaine consumption. Objectives Here, we investigated the effects of NPS in Marchigian Sardinian alcohol-preferring (msP) rats, a rat strain characterized by excessive alcohol consumption comorbid with heightened anxiety and depressive-like phenotypes. Specifically, we evaluated the effect of NPS on operant alcohol self-administration by msP rats compared to Wistar rats. The effect of NPS on cue-induced reinstatement of alcohol seeking in msP rats was also evaluated. Finally, using the open field test (OFT) and the elevated plus maze (EPM), we evaluated the effects of NPS on locomotor activity and anxiety. Results NPS reduced alcohol self-administration but did not affect cue-induced reinstatement in the msP rat. In addition, NPS induced reinstatement of extinguished alcohol seeking in Wistar rats without affecting alcohol intake. In the EPM task, NPS, in accordance with its anxiolytic activity, increased the time spent in the open arm of the arena by msP rats, although this effect was not observed in Wistar rats. Conclusions These data suggest that the effect of NPS is strongly influenced by the genetic background of the animal. In Wistar rats, NPS acts as a pro-arousal agent to promote the reinstatement of alcohol seeking. However, when alcohol drinking is motivated by or associated with a state of pathological anxiety, NPS attenuates alcohol consumption and seeking due to its anxiolytic activity.

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“…In these rats, NOP agonists attenuate home cage alcohol drinking, operant alcohol self-administration, and drug seeking elicited by stress and environmental conditioning factors (Ciccocioppo et al, 2004;Economidou et al, 2006aEconomidou et al, , 2008. The efficacy of NOP agonists on alcohol intake has also been documented in post-dependent outbred Wistar rats whereas they are not effective in nondependent Wistar rats, unless very high doses are used (de Guglielmo et al, 2015a;Economidou et al, 2006a;Kuzmin et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

Kallupi

Scuppa

Guglielmo

et al. 2016

Neuropsychopharmacol

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The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the NOP/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal, and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (− / − ) rats to study the motivation for cocaine, heroin, and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP ( − / − ) rats selfadminister less cocaine (0.25, 0.125, or 0.5 mg/infusion) both under a fixed ratio 1 and a progressive ratio schedule of reinforcement compared with wild-type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP ( − / − ). When NOP ( − / − ) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showed significantly lower drug intake compared with Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP ( − / − ) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol selfadministration in Wt rats but not in NOP ( − / − ) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.

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MT‐7716, a potent NOP receptor agonist, preferentially reduces ethanol seeking and reinforcement in post‐dependent rats

Cited by 48 publications

References 39 publications

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems

Neuropeptide S differently modulates alcohol-related behaviors in alcohol-preferring and non-preferring rats

Genetic Deletion of the Nociceptin/Orphanin FQ Receptor in the Rat Confers Resilience to the Development of Drug Addiction

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