U-50,488H, a selective kappa opioid receptor agonist, ameliorates memory impairments induced by muscarinic autoreceptor agonist, carbachol in mice.
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 micromol/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.
Hiramatsu
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan. mhiramt@meijo-u.ac.jp
Hyodo
T
T
Kameyama
T
T
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D017660:Autoreceptors / Q000819:agonists; D001362:Avoidance Learning / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D017660:Autoreceptors; D018721:Muscarinic Agonists; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D002217:Carbachol