Roles of kappa-opioid receptor agonists in learning and memory impairment in animal models.
The role of kappa-opioid receptor agonists on learning and memory is controversial. In this review, the effects of dynorphin A (1-13) and U-50,488H on learning and memory impairments in mice and rats are summarized. Muscarinic cholinergic antagonists and a nicotinic cholinergic antagonist significantly impaired learning and memory in various behavioral tests. Administration of dynorphin A (1-13) or U-50,488H reversed the impairment of learning and memory. U-50,488H completely blocked the decrease in acetylcholine release induced by mecamylamine, while it only partially blocked the increase of acetylcholine induced by scopolamine. The antagonistic effect of U-50,488H was abolished by pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist. Dynorphin A (1-13) and U-50,488H did not affect the impairment of learning and memory induced by the blockade of NMDA-receptors by dizocilpine ((+)-MK-801. These results suggest that kappa-opioid receptor antagonist reverses the impairment of learning and memory induced by the blockade of cholinergic transmission and abolishes the decrease of acetylcholine release via the kappa-opioid receptor-mediated neuronal system.
Hiramatsu
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan. mhiramt@miejo-u.ac.jp
Kameyama
T
T
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D006801:Humans; D007858:Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced*; D008960:Models, Psychological; D010446:Peptide Fragments / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D010446:Peptide Fragments; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins