Ameliorative effect of vasopressin-(4-9) through vasopressin V1A receptor on scopolamine-induced impairments of rat spatial memory in the eight-arm radial maze

Kenichi Mishima, Hiroshi Tsukikawa, Kenichi Inada, Megumi Fujii, Katsunori Iwasaki, Yoshiaki Matsumoto, Kohji Abe, Takashi Egawa, Michihiro Fujiwara

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In order to clarify the mechanism by which pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2 (vasopressin-(4-9)), a major metabolite C-terminal fragment of [Arg8]-vasopressin (vasopressin-(1-9)), improves learning and memory, we used several different drugs such as an acetylcholine receptor antagonist, a Ca2+/calmodulin-dependent protein kinase II inhibitor, vasopressin receptor antagonists and L-type Ca2+ channel blocker to disrupt spatial memory in rats. Moreover, we examined the effect of vasopressin-(4-9) on acetylcholine release in the ventral hippocampus using microdialysis. Vasopressin-(4-9) (10 fg/brain, i.c.v.) improved the impairment of spatial memory in the eight-arm radial maze induced by scopolamine, pirenzepine and Ca2+/calmodulin -dependent protein kinase II inhibitor. Pirenzepine, a vasopressin V1A receptor antagonist, and L-type Ca2+ channel blocker, but not a vasopressin V2 receptor antagonist, suppressed the effects of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory. Moreover, vasopressin-(4-9) did not affect acetylcholine release in the ventral hippocampus of intact rats or of scopolamine-treated rats as assessed by microdialysis. These results suggest that vasopressin-(4-9) activates vasopressin V1A receptors on the postsynaptic membrane of cholinergic neurons, and induces a transient influx of intracellular Ca2+ through L-type Ca2+ channels to interact with muscarinic M1 receptors. The activation of these processes by vasopressin-(4-9) is critically involved in the positive effect of vasopressin-(4-9) on scopolamine-induced impairment of spatial memory.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalEuropean Journal of Pharmacology
Volume427
Issue number1
DOIs
Publication statusPublished - Sep 7 2001
Externally publishedYes

Keywords

  • Ca
  • Eight-arm radial maze
  • Scopolamine
  • Spatial memory
  • Vasopressin V receptor
  • Vasopressin-(4-9)

ASJC Scopus subject areas

  • Pharmacology

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