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

Abstract

AbstractThe 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. Drug Dev. Res. 54:12–18, 2001. © 2001 Wiley‐Liss, Inc.