Effects of betahistine, a histamine H1 agonist and H3 antagonist, in a light/dark test in mice.
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The effects of betahistine, a histamine H1 agonist and H3 antagonist, were investigated in a light/dark test measuring anxiety in mice. Betahistine significantly decreased the locomotion and rearing in the light and dark zones, shuttle crossing and time spent in the light zone in the light/dark test. These phenomena suggest that betahistine has anxiogenic effects and/or locomotor suppressive effects. Pyrilamine (6 mg/kg) and ketotifen (6 mg/kg), H1-receptor antagonists, antagonized the effects of betahistine (100 mg/kg) on all parameters in the light/dark test but zolantidine (6 mg/kg), an H2-receptor antagonist, augmented its effects on some parameters decreased by betahistine. Especially, it potentiated the decreases by betahistine in the parameters showing anxiety in this test. The decreases in the light/dark test induced by zolantidine (6 mg/kg) plus betahistine (200 mg/kg) were antagonized by pyrilamine (12 mg/kg) but antagonism of the decrease in the time spent in the light zone as a parameter showing anxiety was not significant. These results suggest that the effects via H1 receptors are involved in anxiety in the light/dark test in mice but the other factor may be simultaneously needed for induction of behaviorally detectable anxiogenic effects in this test.