title: Acute and subchronic treatments with selective serotonin reuptake inhibitors increase Nociceptin/Orphanin FQ (NOP) receptor density in the rat dorsal raphe nucleus; interactions between nociceptin/NOP system and serotonin.
abstract: Nociceptin/Orphanin FQ is the endogenous ligand of NOP receptor, formerly referred to as the Opioid Receptor-Like 1 receptor. We have previously shown that NOP receptors were located on serotonergic neurons in the rat dorsal raphe nucleus, suggesting possible direct interactions between nociceptin and serotonin in this region, which is a target for antidepressant action. In the present study, we investigated further the link between Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant treatments and the nociceptin/NOP receptor system. Intraperitoneal administration of the SSRI citalopram induced an increase in NOP-receptor density, measured by autoradiographic [(3)H] nociceptin binding, in the rat dorsal raphe nucleus, from the first to the 21st day of treatment. This effect was also observed with other SSRIs (sertraline, fluoxetine), but not with two tricyclic antidepressants (imipramine, clomipramine) and was abolished by pre-treatment with para-chlorophenylalanine, an inhibitor of serotonin synthesis. Using microdialysis experiments, we demonstrated that NOP-receptor activation by infusion of nociceptin 10(-6) M or 10(-5) M increased the level of extracellular serotonin in the dorsal raphe nucleus. This effect was abolished by co-infusion of the NOP-receptor antagonist UFP 101. These results confirm the existence of reciprocal interactions between serotonin and nociceptin/NOP transmissions in the dorsal raphe nucleus.
authors.affiliation: Unité de Neuropsychopharmacologie de la Dépression, EA 4359, IRIB, Faculté de Médecine-Pharmacie, 22 Bd. Gambetta, 76183 Rouen Cedex 1, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Le Maître
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dourmap
authors.forename: Catherine
authors.initials: C
authors.lastname: Vilpoux
authors.forename: Romain
authors.initials: R
authors.lastname: Leborgne
authors.forename: François
authors.initials: F
authors.lastname: Janin
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Bonnet
authors.forename: Jean
authors.initials: J
authors.lastname: Costentin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leroux-Nicollet
mesh_terms: D000818:Animals; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D018847:Opioid Peptides / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D015283:Citalopram; D018847:Opioid Peptides; D011957:Receptors, Opioid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat