NC-1900, AN ACTIVE FRAGMENT ANALOG OF ARGININE-VASOPRESSIN, IMPROVES LEARNING AND MEMORY DEFICITS INDUCED BY BETA-AMYLOID PROTEIN IN RATS

We have reported that the continuous infusion of beta-amyloid protein- (1-40) into the rat cerebral ventricle produces learning and memory de ficits accompanied by dysfunction in the cholinergic and dopaminergic systems. -asparaginyl-r-seryl-L-prolyl-L-arginylglycinamide (NC-1900), an active fragment analog of arginine vasopressin in the rat brain, i s a stable peptide with a five-fold longer half-life than that of argi nine vasopressin-(4-9). In the present study, we examined the effects of NC-1900 on learning and memory deficits in beta-amyloid protein-(1- 40)-infused rats. The rats were injected subcutaneously with NC-1900 ( 0.1 and 1 ng kg(-1)) once a day throughout the period of behavioral ex amination. In the beta-amyloid protein-infused rats, learning and memo ry in water maze and passive avoidance tasks were impaired compared wi th these in the control rats. NC-1900 prevented the learning and memor y deficits in beta-amyloid protein-infused rats. Moreover, NC-1900 ten ded to increase the choline acetyltransferase activity in the frontal cortex of the beta-amyloid protein-infused rats. These results suggest ed that NC-1900 could be useful for the treatment of patients with Alz heimer's disease. (C) 1998 Elsevier Science B.V. All rights reserved.