Chronic treatment with the selective NOP receptor antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats.
BACKGROUND
The present study was designed to assess the antidepressant effects of UFP-101, a selective nociceptin/orphanin FQ peptide (NOP) receptor antagonist, in a validated animal model of depression: the chronic mild stress (CMS).


RESULTS
UFP-101 (5, 10 and 20 nmol/rat; i.c.v., once a day for 21 days) dose- and time-dependently reinstated sucrose consumption in stressed animals without affecting the same parameter in non-stressed ones. In the forced swimming test, UFP-101 reduced immobility of stressed rats from day 8 of treatment. After a 3-week treatment, rats were killed for biochemical evaluations. UFP-101 abolished increase in serum corticosterone induced by CMS and reverted changes in central 5-HT/5-HIAA ratio. The behavioural and biochemical effects of UFP-101 mimicked those of imipramine, the reference antidepressant drug, administered at the dose of 15 mg/kg (i.p.). Co-administration of nociceptin/orphanin FQ (5 nmol/rat, from day 12 to 21) prevented the effects of UFP-101. Brain-derived neurotrophic factor mRNA and protein in hippocampus were not reduced by CMS nor did UFP-101 modify these parameters.


CONCLUSIONS
This study demonstrated that chronic treatment with UFP-101 produces antidepressant-like effects in rats subjected to CMS supporting the proposal that NOP receptors represent a candidate target for the development of innovative antidepressant drugs.
Vitale
Giovanni
G
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, 41100, Modena, Italy. giovanni.vitale@unimore.it
Ruggieri
Valentina
V
Filaferro
Monica
M
Frigeri
Claudio
C
Alboni
Silvia
S
Tascedda
Fabio
F
Brunello
Nicoletta
N
Guerrini
Remo
R
Cifani
Carlo
C
Massi
Maurizio
M
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid; D013315:Stress, Psychological / Q000188:drug therapy; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming; D013997:Time Factors; D000094942:Nociceptin Receptor
D000928:Antidepressive Agents; D007099:Imipramine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D013395:Sucrose; D000094942:Nociceptin Receptor; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C000722285:Oprl1 protein, rat