Cognition enhancement by the acetylcholine releaser DuP 996

DuP 996, 3,3,‐Bis(4‐pyridinylmethyl)‐1‐phenylindolin‐2‐one, a potent in vitro and in vivo releaser of acetylcholine (ACh), dopamine (DA), and serotonin (5HT) in rat brain, significantly enhanced the performance of rats and mice in several behavioral test procedures. At doses of 0.01–0.1 mg/kg s.c. DuP 996 protected against a hypoxia‐induced passive avoidance deficit in rats. In active avoidance procedures, DuP 996 enhanced acquisition of responses: in rats, at doses between 0.085 and 0.85 mg/kg s.c. and 0.25 and 0.85 mg/kg p.o.; in mice, at doses between 0.85 and 2.5 mg/kg s.c. These effects occurred without any alteration of sensitivity to foot‐shock. In addition, Dup 996 prevented a CO2‐induced retention deficit of a passive avoidance response when administered prior to acquisition testing. In a test for acquisition of lever pressing for food in the rat, DuP 996 increased the proportion of animals acquiring this response. Thus, DuP 996 was active in both the shock‐ and appetitive‐motivated procedures and was shown to enhance performance levels when administered post‐training as well as before training trials. These results suggest that DuP 996 may be useful in the treatment of cognition dysfunction.