STUDY ON ELUCIDATION OF ACTION MECHANISM OF OPIOID PEPTIDES,DYNORPHINS

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The aim of the present study was to elucidate physiological roles of kappa opioid receptor agonists in the learning and memory process, using behavioral and neurochemical procedures. 1) U-50, 488H and dynorphin A (1-13), kappa opioid receptor agonists, improved carbachol-induced impairment of learning and memory in mice and rats in the passive avoidance task. 2) U-50, 488H improved scopolamine- and mecamylamine-induced impairment of learning and memory in the passive avoidance task. 3) Perfusion of carbachol or mecamylamine decreased the extracellular acetyicholine concentration in the rat hippocampus using a microdialysis technique. Dynorphin A (1-13) and U-50, 488H inhibited this decrease in acetyicholine, and nor-BNI, a selective kappa opioid receptor antagonist, prevented these effects. These results suggest that improving effects of kappa opioid receptor agonists on impairment of learning and memory accompanied with improvement of decrease in acetyicholine release in the hippocampus.