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 deficits accompanied by dysfunction in the cholinergic and dopaminergic systems. L-Pyroglutamyl-L-asparaginyl-L-seryl-L-prolyl-L-arginylglycinamide (NC-1900), an active fragment analog of arginine vasopressin in the rat brain, is a stable peptide with a five-fold longer half-life than that of arginine 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 examination. In the beta-amyloid protein-infused rats, learning and memory in water maze and passive avoidance tasks were impaired compared with these in the control rats. NC-1900 prevented the learning and memory deficits in beta-amyloid protein-infused rats. Moreover, NC-1900 tended to increase the choline acetyltransferase activity in the frontal cortex of the beta-amyloid protein-infused rats. These results suggested that NC-1900 could be useful for the treatment of patients with Alzheimer's disease.
Tanaka
T
T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Yamada
K
K
Senzaki
K
K
Narimatsu
H
H
Nishimura
K
K
Kameyama
T
T
Nabeshima
T
T
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001127:Arginine Vasopressin / Q000737:chemistry*; D001522:Behavior, Animal / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005625:Frontal Lobe / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D007276:Injections, Intraventricular; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D009842:Oligopeptides / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; C115056:NC 1900; D009842:Oligopeptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D001127:Arginine Vasopressin; D002795:Choline O-Acetyltransferase; D011761:Pyrrolidonecarboxylic Acid