Antiamnestic Effect of the Two Novel k-Opioid Agonists, VA-100 and VA-101, in the Mouse Passive Avoidance Test

The effects of the administration of the two novel κ-opioid agonists (VA-100, VA-101) on memory processes were evaluated with the mouse passive avoidance 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 prevented nor-binaltorphimine (4.9 μg 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 effective doses, none of the drugs impaired motor coordination, as revealed by the rota-rod test, nor modified spontaneous motility and inspection activity, as revealed by the hole board test. The antiamnesic effect induced by VA-100 and VA-101 was comparable to that exerted by the κ-opioid agonist U-50, 488H, as well as that induced by the nootropic drug piracetam and the cholinesterase inhibitor physostigmine. These results suggest that the activation of κ-opioid receptors plays an important role in the prevention of memory impairment. On these bases, κ-opioid receptor agonists could represent a useful symptomatic treatment for cognitive deficits. © 2001 Wiley-Liss, Inc.