Ameliorative effect of vasopressin-(4-9) through vasopressin V-1A receptoron scopolamine-induced impairments of rat spatial memory in the eight-arm radial maze

In order to clarify the mechanism by which pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH 2 (vasopressin-(4-9)), a major metabolite C-terminal fragment of [Arg(8)]-v asopressin (vasopressin-(1-9)), improves learning and memory, we used sever al different drugs such as an acetylcholine receptor antagonist, a Ca2+/cal modulin-dependent protein kinase II inhibitor, vasopressin receptor antagon ists and L-type Ca2+ channel blocker to disrupt spatial memory in rats. Mor eover, we examined the effect of vasopressin-(4-9) on acetylcholine release in the ventral hippocampus using microdialysis. Vasopressin-(4-9) (10 fg/b rain, i.c.v.) improved the impairment of spatial memory in the eight-arm ra dial maze induced by scopolamine, pirenzepine and Ca2+/calmodulin-dependent protein kinase II inhibitor. Pirenzepine, a vasopressin V-1A receptor anta gonist, and L-type Ca2+ channel blocker, but not a vasopressin V-2 receptor antagonist, suppressed the effects of vasopressin-(4-9) on scopolamine-ind uced impairment of spatial memory. Moreover, vasopressin-(4-9) did not affe ct acetylcholine release in the ventral hippocampus of intact rats or of sc opolamine-treated rats as assessed by microdialysis. These results suggest that vasopressin-(4-9) activates vasopressin V-1A receptors on the postsyna ptic membrane of cholinergic neurons, and induces a transient influx of int racellular Ca2+ through L-type Ca2+ channels to interact with muscarinic M- 1 receptors. The activation of these processes by vasopressin-(4-9) is crit ically involved in the positive effect of vasopressin-(4-9) on scopolamine- induced impairment of spatial memory. (C) 2001 Elsevier Science B.V. All ri ghts reserved.