Potential cognition-enhancing properties of S 9977 in three moenls of amnesia in the mouse

The effects of S 9977 (1,3,7-trimethyl 8-[3-(4-diethylaminocarbonyl-l-piperazinyl) 1-propyl]-3,7-dihydro(1H)2,6-purinedione hydrochloride) on the amnesias induced by scopolamine, diazepam, and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg i.p.) 30 min before or ECS administered immediately after the first session (S1) of the passive avoidance task. S 9977 was studied in a dose range of 0.0312–16 mg/kg administered p.o. 60 min before S1. Retention was measured 24 hr later (S2) in the absence of any treatment. S 9977 was also investigated after repeated administration (twice daily for 3 days and then 60 min before acquisition on the 4th day) using the scopolamine-induced amnesia model. Additional experiments investigated the interactions of the compound with the major behavioral effects of the amnesic treatments, namely scopolamine-induced hyperactivity (activity meter test), diazepam-induced release of punished behavior (four plates test), and ECS-induced convulsion. S 9977 at low doses (0.0312–0.5 mg/kg p.o.) clearly attenuated the memory deficits induced by the three amnesic treatments after acute treatment and no tolerance was observed after repeated treatment in the scopolamine model. S 9977 did not affect either scopolamine-induced hyperactivity, diazepam-induced release of punished behavior, or ECS-induced convulsions. These results point to the specificity of S 9977's antiamnesic activity and suggest that it might be a useful agent for the treatment of memory deficits of different origins in humans. © 1992 Wiley-Liss, Inc.