Different profile of SDZ ENA 713 from other acetylcholinesterase inhibitors to improve cholinergic deficit in basal forebrain-lesioned rats

• Published in: Japanese Journal of Pharmacology Vol. 71; no. suppl.1; p. 98
• Main Authors: Ohara, Tatsuo, Tanaka, Ken-ichi, Fukaya, Hiroaki, Akahane, Noriko, Demura, Nobutaka, Seno, Naoki
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1996
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)36631-4

We previously reported that SDZ ENA 713 (ENA) improved both spatial learning disability and cholinergic dysfunction in basal forebrain (BF)-lesioned rats. The present study was designed to characterize the effects of ENA by comparison with those of Tacrine and physostigmine using behavioral and neurochemical techniques. We prepared memory-impaired rats by injecting ibotenic acid into both sides of the BE. The Morriss water maze test was performed 1 trial per day for 5 consecutive days. The animals were orally treated with ENA and Tacrine two hours and with physostigmine thirty minutes before each task. After finishing the behavioral test, choline acetyltransferase (ChAT) activity was determined in the frontal cortex of the same animals. The BF lesioning markedly impaired the learning ability in the water maze test and ChAT activity in the frontal cortex. ENA (0.2 mg/kg) significantly ameliorated the impaired spatial learning ability and ChAT activity. Physostigmine (0.2 and 0.4 mg/kg) and Tacrine (0.8 and 1.6 mg/kg) significantly improved the learning ability in a similar degree to ENA, but failed to normalize the reduced ChAT activity. These results suggest that the ChAT improving effect seems to be specific to ENA and appears to be based on mechanisms other than the inhibition of acetylcholinesterase.