Effect of the histamine H3-antagonist clobenpropit on spatial memory deficits induced by MK-801 as evaluated by radial maze in Sprague-Dawley rats.
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.
Huang
Yu-Wen
YW
Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Hu
Wei-Wei
WW
Chen
Zhong
Z
Zhang
Li-San
LS
Shen
Hai-Qing
HQ
Timmerman
Henk
H
Leurs
Rob
R
Yanai
Kazuhiko
K
D000704:Analysis of Variance; D000818:Animals; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006633:Histamine Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D006633:Histamine Antagonists; D007093:Imidazoles; D010880:Piperidines; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D016291:Dizocilpine Maleate; D013890:Thiourea; C086108:clobenpropit