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

  title={The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats},
  author={Gwena{\"e}lle Le Pen and Juergen Wichmann and J. -L. Moreau and François Jenck},
The abuse liability of Ro 64-6198, an orphanin FQ (OFQ) receptor full agonist that exhibits anxiolytic properties, was evaluated using an unbiased conditioned place preference (CPP) paradigm in rats. As OFQ is structurally related to opioid peptides and also exhibits anxiolytic-like properties, the effect of Ro 64-6198 on CPP was compared with those of morphine and alprazolam. We show here that neither Ro 64-6198 nor alprazolam exhibited rewarding or aversive properties, whereas morphine… 

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

The findings of this study confirm the potent, ORL-1 receptor-mediated, anxiolytic-like effects of Ro64-6198, extending the findings across three species.

Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence

Evidence is provided that stimulation of the OP4 receptor suppresses acute morphine antinociception, but is not sufficient to inhibit the development of morphine dependence in mice.

The therapeutic potential of nociceptin/orphanin FQ receptor agonists as analgesics without abuse liability.

The present review highlights the recent progress of pharmacological studies of NOP-related ligands in primates and provides new perspectives to establish a translational bridge for understanding the biobehavioral functions of Nop receptors in primates.

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.

Pharmacological Investigation of NOP-Related Ligands as Analgesics without Abuse Liability

These studies further support the therapeutic potential of NOP-related ligands including selective NOP agonists and bifunctional NOP/MOP agonist as effective analgesics in order to achieve strong pain relief without concerns over abuse and safety.

Central administration of nociceptin/orphanin FQ blocks the acquisition of conditioned place preference to morphine and cocaine, but not conditioned place aversion to naloxone in mice

Nociceptin blocks the rewarding properties of drugs in both narcotic analgesic and psychostimulant classes in the mouse, and has only a minor effect on the negative affective state experienced following naloxone administration.

Is the nociceptin (NOP) receptor involved in attenuation of the expression of sensitization to morphine-induced hyperlocomotion in mice?

The results suggest that the NOP receptor may not be critical for the influence of Ro-compounds on the morphine-induced sensitization, or the observed effect may be attributed to one functional subset of this receptor, stimulation of which is not blocked by [Nphe]NC (1-13)NH2.



Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress.

  • F. JenckJ. Moreau O. Civelli
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
It is shown that OFQ plays an important role in higher brain functions because it can act as an anxiolytic to attenuate the behavioral inhibition of animals acutely exposed to stressful/anxiogenic environmental conditions.

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.

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

Place conditioning with cocaine and the dopamine uptake inhibitor GBR12783.

The rewarding and locomotor effects of the specific dopamine uptake inhibitor GBR12783 were compared with those of cocaine and it is suggested that these two properties are, at least in part, separable anatomically or functionally.

Effects of diazepam on conditioned place preference induced by morphine or amphetamine in the rat

Diazepam interferes with the reinforcing properties of amphetamines but not of morphine, which indicates that its effects on morphine and amphetamine CPP were not due to a differential effect on locomotion.

Orphanin FQ: A Neuropeptide That Activates an Opioidlike G Protein-Coupled Receptor

Orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior by binding to its receptor in a saturable manner and with high affinity.