Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats.
Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its effect on locomotion.
Vitale
Giovanni
G
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, I-41100 Modena, Italy. vitale.giovanni@unimore.it
Arletti
Rossana
R
Ruggieri
Valentina
V
Cifani
Carlo
C
Massi
Maurizio
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological; D003345:Corticosterone / Q000032:analysis / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009483:Neuropsychological Tests; D018847:Opioid Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D000097629:Nociceptin
D014151:Anti-Anxiety Agents; D003345:Corticosterone; D018847:Opioid Peptides; D000097629:Nociceptin