Reversal of stress- and CRF-induced anorexia in rats by the synthetic nociceptin/orphanin FQ receptor agonist, Ro 64-6198

  title={Reversal of stress- and CRF-induced anorexia in rats by the synthetic nociceptin/orphanin FQ receptor agonist, Ro 64-6198},
  author={Roberto Ciccocioppo and Michela Biondini and Lorena Antonelli and Juergen Wichmann and François Jenck and Maurizio Massi},
Abstract.Rationale: (1S,3aS)-8-(2,3,3,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro 64-6198), a non-peptidic agonist for the opioid receptor-like1 (ORL1) receptor, exhibits anxiolytic properties in stressful conditions. Objective: The present study was aimed at evaluating whether activation of ORL1 receptors by Ro 64-6198 may reverse the anorectic effect of restraint stress or intracerebroventricular (ICV) CRF injection. Methods: In body restraint experiments… 

Functional antagonism between nociceptin/orphanin FQ (N/OFQ) and corticotropin-releasing factor (CRF) in the rat brain: evidence for involvement of the bed nucleus of the stria terminalis

Evaluating the role of the BST in the functional antagonism between N/OFQ and CRF by examining it at molecular level and in the context of CRF-induced anxiety in the rat suggests that this antagonism may occur within the BST.

MT-7716, a novel selective nonpeptidergic NOP receptor agonist, effectively blocks ethanol-induced increase in GABAergic transmission in the rat central amygdala

Support is provided for an interaction between the nociceptin and GABAergic systems in the CeA and for the anti-alcohol properties of the NOP activation.

Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats

The present study demonstrates that the reinforcing effects of ethanol are markedly blunted by activation of the opioidergic N/OFQ receptor system, and provides evidence of the efficacy of N/ OFQ to prevent reinstatement of ethanol-seeking behaviour elicited by environmental conditioned stimuli.

The pharmacology of Ro 64-6198, a systemically active, nonpeptide NOP receptor (opiate receptor-like 1, ORL-1) agonist with diverse preclinical therapeutic activity.

Preclinical data indicate that Ro 64-6198 may have broad clinical uses, such as in treating stress and anxiety, addiction, neuropathic pain, cough, and anorexia, and it has subnanomolar affinity for the NOP receptor and is at least 100 times more selective for theNOP receptor over the classic opioid receptors.



A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat.

These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphan in F Q/nOCiceptin in adaptive behavioral fear responses to stress.

Nociceptin/orphanin FQ inhibits stress- and CRF-induced anorexia in rats

Findings provide original evidence that NC attenuates stress-induced anorexia, presumably by acting as a functional CRF antagonist, and suggest that the effect of NC is selective forAnorexia induced by stress or CRF.

The role of CRF2 receptors in corticotropin‐releasing factor‐and urocortin‐induced anorexia

The data suggest that down-regulation of CRF2 receptors selectively attenuates CRF-and UCN-induced anorexia and hypothalamo-pituitary-adrenocortical activation in rats.

CRF-Deficient Mice Respond Like Wild-Type Mice to Hypophagic Stimuli

Verapamil and indomethacin attenuate endotoxin-induced anorexia

Effect of nociceptin on alcohol intake in alcohol-preferring rats

The results of the present study suggest that the brain NC mechanisms may represent an interesting target of pharmacological interventions for the treatment of alcoholism.

Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more

Orphanin FQ is a functional anti-opioid peptide

Pharmacological characterization of the nociceptin receptor mediating hyperphagia: identification of a selective antagonist

The findings suggest that [F/G)]NC(1–13)NH2, which has been reported to act as a NC receptor antagonist in peripheral tissues, be- haves as a full agonist at the central NC receptors controlling feeding, to study the physiological and pathophysiological role of NC in feeding behaviour.

Nociceptin prevents stress‐induced ethanol‐but not cocaine‐seeking behavior in rats

The hypothesis that the NC system participates in the regulation of behavioral responses to stress, and that drugs interacting with NC receptors may have therapeutic potential for the treatment of stress-induced alcohol-seeking behavior and relapse, is supported.