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

Nociceptin/orphanin FQ (N/OFQ) is an endogenous neuropeptide of 17 amino acids, related to opioid peptides but with its own receptor, distinct from conventional opioid receptors, the ORL1 or NOP receptor. The NOP receptor is a G protein-coupled receptor which activates Gi/o proteins and thus induces an inhibition of neuronal activity. The peptide and its receptor are widely expressed in the central nervous system with a high density of receptors in regions involved in learning and memory. This review describes 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. We also discuss the role of endogenous N/OFQ release in the modulation of learning and memory. Finally we propose several putative neuronal mechanisms taking place at the level of the hippocampus and amygdala and possibly underlying the behavioral amnestic or promnesic effects of NOP ligands.