Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test.
The present study investigated the effects of nociceptin, the peptide nociceptin receptor antagonist, [Nphe(1)]-nociceptin (1-13)-NH(2), and the non-peptide antagonist, J-113397, in the mouse forced swimming test, an animal model used for the screening of potential antidepressant drugs. Additional studies were performed with naloxone to exclude effects on traditional opioid receptors. Intracerebroventricular (ICV) administration of nociceptin (0.01-1 nmole) was devoid of any activity in the mouse forced swimming test, as was intraperitoneal (i.p.) administration of naloxone (1-10 mg/kg). ICV treatment with [Nphe(1)]-nociceptin (1-13)-NH(2) (25 nmole and 50 nmole) induced significant antidepressant-like activity ( P<0.01), as did administration of J-113397 (20 mg/kg, i.p; P<0.05). Open field analysis revealed that acute treatment with these molecules did not induce significant changes in locomotor activity at the doses tested. These results suggest that nociceptin, and its receptor, may play a role in depressive disorders and that the nociceptin system could represent a novel target for the development of new antidepressant drugs.
Redrobe
John P
JP
Douglas Hospital Research Centre, McGill University, 6875 LaSalle Boulevard, Verdun, QC H4H 1R3, Canada.
Calo'
Girolamo
G
Regoli
Domenico
D
Quirion
Rémi
R
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011957:Receptors, Opioid; D013550:Swimming; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000928:Antidepressive Agents; D001562:Benzimidazoles; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D010880:Piperidines; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C402921:J 113397; C403776:nociceptin-(1-13)-NH2, NPhe(1)-; C000722287:Oprl1 protein, mouse