Orphanin FQ, a novel neuropeptide with anti-stress-like activity

Potential anxiolytic-like properties of intracerebroventricular (i.c.v.) infusion of orphanin FQ (OFQ), a recently discovered neuropeptide, were investigated in the mouse defense test battery, a well-validated anxiolytic screening test. Zn this model, Swiss mice are directly confronted with a natural threat (a rat) as well as situations associated with this threat. Primary measures taken during and after rat confrontation were flight, risk assessment, defensive attack and escape attempts. Unlike the anxiolytic drug diazepam (3-10 mu g/5 mu l, i.c.v.), which affected all defensive responses, OFQ (0.3-3 nM/5 mu l) only clearly reduced defensive upright postures and biting reactions. Subjects displayed these latter defensive behaviors upon forced contact with the threat stimulus, a situation which is considered to be highly stressful. These results suggest that the OFQ system may not be primarily involved in anxiety-related responses including cognitive aspects (i.e., risk assessment), while it may play a role in the adaptative responses to unavoidable or extreme stress stimuli. (C) 1999 Published by Elsevier Science B.V. All rights reserved.