Ming Chang, Hiroshi Saito and Kazuho Abe (*)
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences,
The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan
(*) To whom correspondence should be addressed.
Abstract: We investigated the effect of cimetidine, a clinically
used H2-receptor antagonist, on the induction of long-term potentiation
(LTP) in the dentate gyrus of anesthetized rats. Intracerebroventricular
injection of cimetidine (50 - 100 nmol) inhibited the induction of LTP in
a dose-dependent manner. The inhibitory effect of cimetidine was not mimicked
by other H2-receptor antagonists (ranitidine, famotidine) or the H1-receptor
antagonist diphenhydramine or the H3-receptor antagonist thioperamide. These
results suggest that cimetidine inhibits hippocampal synaptic plasticity
by a novel brain mechanism unrelated to H1, H2 or H3 receptors.
Keywords: Cimetidine, Long-term potentiation, Hippocampus