title: Endogenous nociceptin/orphanin-FQ in the dorsal hippocampus facilitates despair-related behavior.
abstract: Nociceptin/orphanin-FQ (N/OFQ) peptide and its receptor (NOP: N/OFQ opioid peptide receptor) are highly expressed in the hippocampus, but their functional role remains poorly understood. We recently showed that hippocampal N/OFQ inhibits learning and memory abilities in mice. Here, we investigated whether the endogenous peptide also regulated emotional responses at the level of the hippocampus. Bilateral infusions of the selective NOP receptor antagonist, UFP-101 (1-3 nmol/side), into the dorsal hippocampus produced antidepressant-like effects in the mouse forced swim and tail suspension tests comparable with those obtained with the prototypical antidepressant, fluoxetine (10-30 mg/kg, intraperitoneal). In the light-dark test, neither UFP-101 (1-3 nmol/side) nor N/OFQ peptide (1-3 nmol/side) modified anxiety measures when injected at behaviorally active doses in the dorsal hippocampus. These findings show a clear dissociation in the involvement of hippocampal N/OFQ system in anxiety- and despair-related behaviors. We conclude that the dorsal hippocampus is a brain region in which there is an important N/OFQ modulation of mnemonic processes and adaptive emotional responses associated to despair states.
authors.affiliation: Université de Strasbourg, Strasbourg, F-67000 France.
authors.forename: Celia
authors.initials: C
authors.lastname: Goeldner
authors.forename: David
authors.initials: D
authors.lastname: Reiss
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: Abdel-Mouttalib
authors.initials: AM
authors.lastname: Ouagazzal
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003623:Dark Adaptation / Q000187:drug effects; D003863:Depression / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D019417:Hindlimb Suspension / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018847:Opioid Peptides / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013141:Spiro Compounds / Q000009:adverse effects; D013550:Swimming / Q000523:psychology; D000097629:Nociceptin
chemical_list: D007093:Imidazoles; D018847:Opioid Peptides; D013141:Spiro Compounds; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C408068:Ro 64-6198