TY - JOUR
T1 - Effect of the histamine H3-antagonist clobenpropit on spatial memory deficits induced by MK-801 as evaluated by radial maze in Sprague-Dawley rats
AU - Huang, Yu Wen
AU - Hu, Wei Wei
AU - Chen, Zhong
AU - Zhang, Li San
AU - Shen, Hai Qing
AU - Timmerman, Henk
AU - Leurs, Rob
AU - Yanai, Kazuhiko
PY - 2004/5/5
Y1 - 2004/5/5
N2 - This study was performed to investigate whether or not the histamine H 3-antagonist clobenpropit can ameliorate spatial memory deficits induced by MK-801 (0.3μg per site) as evaluated by an eight-arm radial maze task of rats. A bilateral intrahippocampal (i.h.) injection of clobenpropit (5, 10μg 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 (2.5μg per site), a selective H3-agonist. α-Fluoromethylhistidine (FMH, 25μg 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 H1-antagonist pyrilamine, but not the H 2-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.
AB - This study was performed to investigate whether or not the histamine H 3-antagonist clobenpropit can ameliorate spatial memory deficits induced by MK-801 (0.3μg per site) as evaluated by an eight-arm radial maze task of rats. A bilateral intrahippocampal (i.h.) injection of clobenpropit (5, 10μg 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 (2.5μg per site), a selective H3-agonist. α-Fluoromethylhistidine (FMH, 25μg 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 H1-antagonist pyrilamine, but not the H 2-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.
KW - Clobenpropit
KW - Endogenous histamine
KW - Learning
KW - MK-801
KW - Maze
KW - Reference memory
KW - Working memory
UR - http://www.scopus.com/inward/record.url?scp=3042848352&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042848352&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2003.09.002
DO - 10.1016/j.bbr.2003.09.002
M3 - Article
C2 - 15084444
AN - SCOPUS:3042848352
VL - 151
SP - 287
EP - 293
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 1-2
ER -