Opioid receptor-like 1 (NOP) receptors in the rat dorsal raphe nucleus: evidence for localization on serotoninergic neurons and functional adaptation after 5,7-dihydroxytryptamine lesion.
A high density of opioid receptor-like 1 (ORL1) receptor (also referred to as NOP receptor) is found in limbic areas and in regions containing monoamines, which are implicated in emotional activity and physiopathology of depression and anxiety. We aimed at defining precisely the localization of ORL1 receptors in dorsal raphe nucleus, by means of a lesion strategy and autoradiographic studies. In control rats, [3H]nociceptin and nociceptin-stimulated [35S]GTPgammaS bindings were found to be correlated in several brain regions. We performed in rats a selective destruction of serotoninergic neurons by surgical stereotaxic injection of 5,7-dihydroxytryptamine (5,7-DHT) in dorsal raphe nucleus. This led to a marked decrease in serotonin contents in striata and frontal cortices (about -60%) and in autoradiographic [3H]citalopram binding in posterior regions. In dorsal raphe nucleus, [3H]nociceptin binding was decreased to the same extent as [3H]citalopram binding, whereas it was unchanged in the other regions studied. Nevertheless, in the dorsal raphe, nociceptin-stimulated [35S]GTPgammaS binding was decreased to a lesser extent than [3H]nociceptin binding in 5,7-DHT-lesioned rats. The ratio between nociceptin-stimulated [35S]GTPgammaS binding and [3H]nociceptin binding was significantly increased in 5,7-DHT-lesioned rats compared with controls in this region. These data demonstrate 1) that ORL1 receptors are located on serotoninergic neurons in the dorsal raphe nucleus and 2) that, after a lesion, the functionality of remaining ORL1 receptors appears to be up-regulated, which could correspond to a compensatory mechanism.
Le Maître
Erwan
E
Unité de Neuropsychopharmacologie Expérimentale, CNRS FRE 2735, IFRMP No. 23, Faculté de Médecine-Pharmacie, Rouen, France.
Vilpoux
Catherine
C
Costentin
Jean
J
Leroux-Nicollet
Isabelle
I
D015116:5,7-Dihydroxytryptamine; D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D015283:Citalopram / Q000378:metabolism / Q000494:pharmacology; D003714:Denervation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D018847:Opioid Peptides / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology; D013462:Sulfur Radioisotopes; D014316:Tritium; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D015116:5,7-Dihydroxytryptamine; D015283:Citalopram; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018847:Opioid Peptides; D011957:Receptors, Opioid; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D013462:Sulfur Radioisotopes; D014316:Tritium; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat