Dynorphin A (2-13) improves mecamylamine-induced learning impairment accompanied by reversal of reductions in acetylcholine release in rats.
Accumulating evidence indicates that the endogenous opioid peptides dynorphin A (1-17) and synthetic dynorphin A (1-13) interact not only with opioid receptors but also with as yet poorly characterized non-opioid binding sites. Dynorphin A (1-13) improved impairments of learning and memory via not only kappa-opioid receptor-mediated, but also 'non-opioid' mechanisms. In the present study, the effects of des-tyrosine(1) dynorphin A (2-13) as a non-opioid metabolite of dynorphin A, and dynorphin A (1-13) on mecamylamine-induced impairment of the acquisition of learning in rats were investigated using a step-through type passive avoidance task. Further, hippocampal acetylcholine release was examined using in vivo microdialysis. Mecamylamine significantly shortened the step-through latency when given 30 min before the acquisition trial. Not only dynorphin A (1-13) but also dynorphin A (2-13) attenuated the mecamylamine-induced impairment of the acquisition of learning. The effect of dynorphin A (2-13) was not blocked by pre-treatment with nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist. Dynorphin A (2-13) completely abolished the decrease in the extracellular acetylcholine concentration induced by mecamylamine and this effect was not blocked by nor-BNI. Taken together with our previous findings, the present results may indicate that dynorphin A (2-13) improves impairment of learning and/or memory in 'non-opioid' mechanisms and dynorphin A (1-13) ameliorates impairment of the acquisition of learning via not only kappa-opioid receptor-mediated mechanisms but also 'non-opioid' mechanisms, by regulating the release of extracellular acetylcholine.
Hiramatsu
Masayuki
M
Laboratory of Neuropsychopharmacology, Graduate School of Environmental and Human Sciences, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan. mhiramt@ccmfs.meijo-u.ac.jp
Watanabe
Eri
E
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D007839:Functional Laterality; D006624:Hippocampus / Q000502:physiology; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D007859:Learning Disabilities / Q000503:physiopathology*; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology*; D017551:Microdialysis; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009292:Narcotic Antagonists; C051844:norbinaltorphimine; D009271:Naltrexone; D008464:Mecamylamine; D004399:Dynorphins; D000109:Acetylcholine