Effects or SDZ ENA-713 on choline acetyltransferase activity and muscarinic acetylcholine receptor binding in the brains of learning impaired rats

• Published in: Japanese Journal of Pharmacology Vol. 67; no. suppl.2; p. 306
• Main Authors: Tanaka, Ken-ichi, Oh-hara, Tatsuo, Fukaya, Hiroaki, Demura, Nobutaka, liniura, Akiko, Seno, Naoki
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1995
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)47187-4

It has been shown that SDZ ENA-713 (ENA), a centrally acting acetylcholinesterase inhibitor, improved learning disability of behavioral tasks in animal models. In the present study, we examined that effects of ENA on choline acetyltransferase (ChAT) activity and muscarinic acetylcholine receptor (mACh-R) binding in the frontal cortex and hippocampus of basal forebrain (BF)-lesiond rats and aged (26 month-old) rats. ChAT activity and mACh-R binding ability were determined by Funnums method using 「^^3 H」-acetyl CoA and by radiolabeled receptor assay using 「^^3 H」-QNB. ENA was given to rats by single, repeated (6 days) or chronic (5 weeks) administration. In the BF-lesioned rats, ChAT activity was significantly decreased in the frontal cortex. mACh-R binding ability was not changed. The reduction in ChAT activity was markedly prevented by the repeated administration of ENA, but not by the single administration. In the case of aged rats, the chronic administration of ENA recovered aging-induced decrease in ChAT activity of the frontal cortex and hippocampus. Cortical mACh-R binding ability was decreased without any change in dffinity, but this decrease was also inhibited by ENA. These results indicate that ENA ameliorates the cholinergic dysfunctions of our animal models.