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- W2080690616 abstract "Histaminergic neurons are activated by histamine H3 receptor (H3R) antagonists, increasing histamine and other neurotransmitters in the brain. The prototype H3R antagonist thioperamide increases locomotor activity and anxiety-like behaviours; however, the mechanisms underlying these effects have not been fully elucidated. This study aimed to determine the mechanism underlying H3R-mediated behavioural changes using a specific H3R antagonist, JNJ-10181457 (JNJ). First, we examined the effect of JNJ injection to mice on the concentrations of brain monoamines and their metabolites. JNJ exclusively increased Nτ-methylhistamine, the metabolite of brain histamine used as an indicator of histamine release, suggesting that JNJ dominantly stimulates the release of histamine release but not of other monoamines. Next, we examined the mechanism underlying JNJ-induced behavioural changes using open-field tests and elevated zero maze tests. JNJ-induced increase in locomotor activity was inhibited by α-fluoromethyl histidine, an inhibitor of histamine synthesis, supporting that H3R exerted its effect through histamine neurotransmission. The JNJ-induced increase in locomotor activity in wild-type mice was preserved in H1R gene knockout mice but not in histamine H2 receptor (H2R) gene knockout mice. JNJ-induced anxiety-like behaviours were partially reduced by diphenhydramine, an H1R antagonist, and dominantly by zolantidine, an H2R antagonist. These results suggest that H3R blockade induces histamine release, activates H2R and elicits exploratory locomotor activity and anxiety-like behaviours." @default.
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- W2080690616 date "2014-06-01" @default.
- W2080690616 modified "2023-10-18" @default.
- W2080690616 title "Mechanism of the histamine H3 receptor-mediated increase in exploratory locomotor activity and anxiety-like behaviours in mice" @default.
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- W2080690616 doi "https://doi.org/10.1016/j.neuropharm.2014.02.003" @default.
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