This study was performed to investigate whether or not the
histamine H3-antagonist
clobenpropit can ameliorate spatial memory deficits induced by
MK-801 (0.3 microg per site) as evaluated by an eight-arm radial maze task of rats. A bilateral intrahippocampal (i.h.) injection of
clobenpropit (5, 10 microg per site, dose-dependent) markedly improved the working and reference
memory deficits induced by
MK-801. Its ameliorating effect was potentiated by
histidine, but completely antagonized by
immepip (2.5 microg per site), a selective H3-agonist.
alpha-Fluoromethylhistidine (FMH, 25 microg per site), a selective
histidine decarboxylase inhibitor prevented the ameliorating effect of
clobenpropit on the working memory deficits induced by
MK-801. In addition, the H(1-antagonist
pyrilamine, but not the H2-antagonist
cimetidine, also inhibited the procognitive effects of
clobenpropit. Both FMH and
pyrilamine did not significantly modulate the effect of
clobenpropit on reference memory. Therefore, the results of this study suggest that the procognitive effects of
clobenpropit in
MK-801-induced working memory deficits is mediated by increasing endogenous histamine release. In addition, the ameliorating effect of
clobenpropit on reference memory might be due to the increased release of
neurotransmitters other than
histamine.