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

  title={A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory},
  author={G. A. Higgins and JN Kew and J. Grayson Richards and Hiroshi Takeshima and François Jenck and Geo Adam and Juergen Wichmann and J. A. Kemp and A. J. Grottick},
  journal={European Journal of Neuroscience},
Using a combination of the selective opioid receptor‐like1 (ORL1) receptor agonist, Ro 64‐6198, and orphanin FQ/nociceptin (OFQ/N) peptide knockout (KO) mice, the influence of OFQ/N on cognition has been studied in the rodent. In wild type, C57BL/6J mice, Ro 64‐6198 (0.3–1 mg/kg i.p.) impaired the acquisition of spatial learning in the Morris water maze, although a mild neurological impairment was evident which complicated precise interpretation. In Lister hooded rats, Ro 64‐6198 (6 mg/kg i.p… 

Nociceptin and the NOP receptor in aversive learning in mice

Effects of nociceptin/orphanin FQ in the acquisition of contextual and tone fear conditioning in rats.

The data support the negative role of N/OFQ in the acquisition of aversively motivated tasks, which encompass a spatial component and depend on the hippocampus.

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.


A novel mutant rat lacking OPr without compensatory changes in , and opioid eceptors is presented and it is anticipated that this mutant rat will have heurisic value to further understand the function of NOPr.

The Nociceptin/Orphanin FQ System and the Regulation of Memory.

The consequences of the pharmacological manipulation of the N/OFQ system by NOP receptor ligands on learning processes and on the consolidation of various types of long-term memory are described.

Distinct effects of nociceptin analogs on scopolamine-induced memory impairment in mice.




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

Characterization of the locomotor activity-inhibiting effect of nociceptin/orphanin FQ in mice

It is demonstrated that NC inhibits LA in mice by activating OP4 receptor sites using NC receptor (OP4) agonist and a pure antagonist of OP4 sites, respectively.

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.

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

Facilitation of long-term potentiation and memory in mice lacking nociceptin receptors

It is shown that mice lacking the nociceptin receptor possess greater learning ability and have better memory than control mice, and that the receptor-deficient mice showed larger long-term potentiation in the hippocampal CA1 region thancontrol mice.

Effects of nocistatin on nociceptin-induced impairment of learning and memory in mice.

Targeted disruption of the orphanin FQ/nociceptin gene increases stress susceptibility and impairs stress adaptation in mice.

OfQ/N appears to be crucially involved in the neurobiological regulation of stress-coping behavior and fear.

Pharmacology of nociceptin and its receptor: a novel therapeutic target

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.

Orphanin FQ/nociceptin inhibits synaptic transmission and long-term potentiation in rat dentate gyrus through postsynaptic mechanisms.

It is demonstrated that OFQ may negatively modulate synaptic transmission and plasticity in the dentate gyrus through postsynaptic mechanisms, including hyperpolarization of granule cells as well as inhibition of the function of post synapse NMDA receptors/channels in dentate granule Cells.