Preventive effect of chotosan, a Kampo medicine, on transient ischemia-induced learning deficit is mediated by stimulation of muscarinic M1 but not nicotinic receptor.
We have previously shown using a water maze task that transient 2 vessel occlusion (T2VO) induced learning deficit in mice and that the deficit was prevented by pre-treatment of mice with chotosan, a Kampo prescription. In this study, we investigated the mechanism underlying the preventive effect of chotosan on T2VO-induced learning deficit. Chotosan administration 1 h before T2VO operation prevented learning impairment. The extract of Uncaria, a major constituent of chotosan, also had a protective effect on learning impairment in T2VO mice, whereas Uncaria-free chotosan had no beneficial effect on maze performance of T2VO mice. The ameliorative effect of chotosan was blocked by pirenzepine, a muscarinic M1 antagonist, but not by mecamylamine, a nicotinic receptor antagonist. Acetylcholine (ACh) content in the hippocampus of T2VO mice was significantly lower than that in the hippocampus of sham-operated control mice. Chotosan and Uncaria administration attenuated T2VO-induced reduction of ACh levels in the brain. These results suggest that the preventive effect of chotosan on transient ischemia-induced learning impairment is mainly attributable to the effect of Uncaria and that the ameliorative effect is mediated by stimulation of muscarinic M1 receptor.
Zhao
Qi
Q
Division of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University; 2630 Sugitani, Toyama 930-0194, Japan.
Murakami
Yukihisa
Y
Tohda
Michihisa
M
Watanabe
Hiroshi
H
Matsumoto
Kinzo
K
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects*; D020835:Medicine, Kampo; D051379:Mice; D008813:Mice, Inbred ICR; D043643:Receptor, Muscarinic M1 / Q000819:agonists*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D004365:Drugs, Chinese Herbal; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; C120250:choto-san; D000109:Acetylcholine