Morphine has been shown to alter several behavioural processes. We aimed to investigate the effects of intracerebroventricular (i.c.v.) morphine on anxiety, memory retrieval and locomotor activity in rats and to elucidate the possible involvement of the vasopressinergic system and the nitric oxide (NO) pathway in these effects. Rats were pretreated with morphine (0.5, 5, 50 mu g/5 mu l; i.c.v.) or saline (5 mu l; i.c.v.) 30 min before the elevated plus maze test, the probe trial of the Morris water maze and the open field test. Morphine (5 mu g/5 mu l; i.c.v.) induced significant anxiolytic effects in the elevated plus maze. None of the doses of morphine produced any effects in the probe trial of the Morris water maze and the open field. Pretreatment with an arginine vasopressin (AVP) V-1 receptor antagonist (25, 125 ng/5 mu l; i.c.v.), an AVP V-2 receptor antagonist (25, 125 ng/5 mu l, i.c.v.), or L-NAME, an NO synthase inhibitor (5, 25 mu g/5 mu l; i.c.v.) 30 min before morphine significantly prevented the anxiolytic effects of morphine. These results suggest that i.c.v. morphine has significant anxiolytic effects, probably mediated by both vasopressinergic system and NO pathway, but has no effect on memory retrieval or locomotor activity, at least at the applied doses. (c) 2006 Elsevier Inc. All rights reserved.