Nociceptin/orphanin FQ reverses mecamylamine-induced learning and memory impairment as well as decrease in hippocampal acetylcholine release in the rat.
Nociceptin/orphanin FQ is an endogenous neuropeptide that plays important roles in several physiological functions including pain, anxiety, locomotion, learning, and memory. We previously reported that low doses of nociceptin improved the scopolamine-induced impairment of learning and memory in the passive avoidance test and the spontaneous Y-maze alternation task in mice. In the present study, the effects of nociceptin on learning and memory impairment as well as the decrease in acetylcholine release induced by mecamylamine were investigated in rats. Mecamylamine (49 micromol/kg, s.c.), a nicotinic acetylcholine receptor antagonist, impaired learning and memory in the step-through type passive avoidance test and decreased acetylcholine release in the hippocampus, as determined by in vivo microdialysis. The administration of nociceptin (10 fmol/rat, i.c.v.) reversed the impairment of learning and memory and blocked the decrease in acetylcholine release induced by mecamylamine. This ameliorating effect on the mecamylamine-induced impairment of learning and memory was not blocked by [NPhe(1)]nociceptin(1-13)NH(2) (1 nmol/rat, i.c.v.), an opioid receptor-like 1 (NOP) receptor antagonist. These results suggest that nociceptin improves the impairment of learning and memory as well as decrease in acetylcholine release induced by mecamylamine, and that these effects may not be mediated by NOP receptors.
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
Miwa
Masaya
M
Hashimoto
Kazuki
K
Kawai
Satoko
S
Nomura
Nao
N
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D017551:Microdialysis; D009292:Narcotic Antagonists; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000109:Acetylcholine; D008464:Mecamylamine; D009292:Narcotic Antagonists; D018733:Nicotinic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat