Antiamnesic effect of the two novel kappa-opioid agonists, VA-100 and VA-101, in the mouse passive avoidance test

The effects of the administration of the two novel kappa -opioid agonists ( VA-100, VA-101) on memory processes were evaluated with the mouse passive a voidance test. The administration of VA-100 (50-100 mg kg(-1) p.o.) and VA- 101 (100 mg kg(-1) p.o.) administered 20 min before the training session pr evented nor-binaltorphimine (4.9 mug per mouse i.c.v.), scopolamine (1.5 mg kg(-1) i.p.), mecamylamine (20 mg kg(-1) i.p.), diphenhydramine (20 mg kg( -1) i.p.), and baclofen (2 mg kg(-1) i.p.) amnesia. At the highest effectiv e doses, none of the drugs impaired motor coordination, as revealed by the rota-rod test, nor modified spontaneous motility and inspection activity, a s revealed by the hole board test. The antiamnesic effect induced by VA-100 and VA-101 was comparable to that exerted by the kappa -opioid agonist U-5 0, 488H, as well as that induced by the nootropic drug piracetam and the ch olinesterase inhibitor physostigmine. These results suggest that the activa tion of kappa -opioid receptors plays an important role in the prevention o f memory impairment. On these bases. kappa -opioid receptor agonists could represent a useful symptomatic treatment for cognitive deficits. (C) 2001 W iley-Liss, Inc.