Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species

  title={Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species},
  author={Geoffrey B. Varty and Lynn A. Hyde and Robert A. Hodgson and S. X. Lu and Martha F. McCool and Tatiana M. Kazdoba and Robert A. Del Vecchio and Donald H. Guthrie and Annamarie J. Pond and Michael E. Grzelak and X. Z. Xu and Walter A. Korfmacher and Deen Bandhu Tulshian and Eric M. Parker and Guy A Higgins},
RationalePrevious studies have demonstrated behaviors indicative of anxiolysis in rats pretreated with the nociceptin receptor (opioid receptor like-1, ORL-1) agonist, Ro64-6198.ObjectivesThe aim of this study was to examine the effects of Ro64-6198 in anxiety models across three species: rat, guinea pig, and mouse. In addition, the receptor specificity of Ro64-6198 was studied, using the ORL-1 receptor antagonist, J-113397, and ORL-1 receptor knockout (KO) mice. Finally, neurological studies… 

The effects of nociceptin/orphanin FQ receptor agonist Ro 64-6198 and diazepam on antinociception and remifentanil self-administration in rhesus monkeys

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A rather unique behavioral profile since the activation or the blockade of a given neuropeptide receptor produces, in most of the cases, both antidepressant- and anxiolytic-like effects.

Characterization of the Discriminative Stimulus Effects of a NOP Receptor Agonist Ro 64-6198 in Rhesus Monkeys

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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

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Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test

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Effects of Ro 64-6198 in nociceptin/orphanin FQ-sensitive isolated tissues

A physiological heterogeneity in OP4 receptors across tissues and species is suggested and may explain why, when tested in vivo, Ro 64-6198 mimics the potent anxiolytic effect of NC better in the rat than in the mouse.

Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological function

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.

A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory

A bi‐directional effect of OFQ/N containing systems on aspects of cognitive behaviour, particularly those elements associated with hippocampal function are suggested, consistent with a likely modulatory role of OFZ/N on hippocampal and associated cortical circuitry.

The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats

It is shown here that neither Ro 64-6198 nor alprazolam exhibited rewarding or aversive properties, whereas morphine induced a pronounced CPP, suggesting that this new class of anxiolytic drugs is devoid of the risk for potential non-medical use and dependence.

The molecular and behavioral pharmacology of the orphanin FQ/nociceptin peptide and receptor family.

The isolation of an opioid receptor-related clone soon led to the isolation and characterization of a new neuropeptide, termed orphanin FQ or nociceptin (OFQ/N). This heptadecapeptide binds to the

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New advances have contributed to better understanding of the pathophysiological role of the NC/OP4 system, and ultimately will help to identify the therapeutic potential of new OP4 receptor ligands.