U-50,488H, a selective kappa opoid receptor agonist, ameliorates memory impairments induced by muscarinic autoreceptor agonist, carbachol in mice

Abstract

We investigated whether carbachol, a muscarinic receptor agonist, induces learning and memory impairments, and U-50,488H, a selective kappa opioid receptor agonist, ameliorates the impairments of learning and memory using a step-down type passive avoidance task in mice. Carbachol induced a dose-related dual response. Carbachol (3 nmol/mouse, i.c.v.) significantly shortened the step-down latency, while lower (1 nmol) and higher (10 nmol) doses of carbachol did not induce learning and memory impairments. U-50,488H (0.64 μmol/kg, s.c.) significantly improved carbachol-induced impairments of learning and memory. These findings suggest that kappa opioid receptor agonists ameliorate learning and memory impairments which may associate with dysfunction of presynaptic cholinergic neurons.