Ameliorative effect of NC-1900, a new AVP 4–9 analog, through vasopressin V 1A receptor on scopolamine-induced impairments of spatial memory in the eight-arm radial maze

Abstract

The mechanism by which NC-1900, a new pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH 2 (AVP 4–9) analog, improves spatial memory in rats using an eight-arm radial maze was examined. Even at very low doses (0.2 ng/kg for s.c., 1 μg/kg for p.o., 1 fg for i.c.v.) NC-1900 improved scopolamine-induced impairment of spatial memory. NC-1900 (1 ng/kg, s.c.) also improved impairment of spatial memory induced by pirenzepine, a muscarinic 1 (M 1) receptor antagonist, and by KN-62, a Ca 2+/calmodulin (CaM)-dependent protein kinase II inhibitor. [Pmp 1, Tyr(Me) 2]-Arg 8-vasopressin, a vasopressin 1A (V 1A) receptor antagonist, and nicardipine, L-type Ca 2+ blocker, but not OPC-31260, a V 2 antagonist, suppressed the effect of NC-1900 on scopolamine-induced impairment of spatial memory. A microdialysis study showed that NC-1900 did not affect acetylcholine release in the ventral hippocampus (VH) of intact rats or of scopolamine-treated rats. NC-1900 (1 μM) increased [Ca 2+] i in the VH than in the dorsal hippocampus (DH). Pretreatment with nicardipine (1 μM) and Ca 2+-free conditions inhibited the NC-1900-induced [Ca 2+] i response in the VH. Whereas co-administration of NC-1900 (1 μM) and carbachol (500 μM) increased [Ca 2+] i in the VH. Moreover, nicardipine concentration-dependently inhibited the increase in [Ca 2+] i induced by the co-administration of NC-1900 and carbachol in the VH. These results suggest that NC-1900 activates the V 1A receptor at the postsynaptic cholinergic nerve, and causes a transient influx of intracellular Ca 2+ through L-type Ca 2+ channels, to interact with the M 1 receptor. The activation of these Ca 2+-dependent processes induced by NC-1900 may be involved in the positive effect of NC-1900 on scopolamine-induced impairment of spatial memory.