The behavioral and biochemical effects of thioperamide, a histamine H3-receptor antagonist, in a light/dark test measuring anxiety in mice.
We investigated the effects of thioperamide, a histamine H3-receptor antagonist, in a light/dark test measuring anxiety in mice. Thioperamide (20 mg/kg) slightly affected the locomotion and time spent in a light zone, and shuttle crossing. However, the decreases of these parameters were significant only when the animals were pretreated with zolantidine, a histamine H2-receptor antagonist. Moreover, the decreased parameters induced by the combination of thioperamide and zolantidine were reversed by pretreatment with pyrilamine, a histamine H1-receptor antagonist. These data suggest that thioperamide induces the release of neuronal histamine, which in turn stimulates both H1- and H2-receptors to produce the anxiogenic effect. The stimulation of histamine H1-receptors may mediate the anxiety, while H2-receptors may play a role in masking the anxiogenic effect. Thus, the present study suggests the involvement of endogenous neuronal brain histamine in anxiety. In the biochemical study, a previous report showed that thioperamide accelerated the release of neuronal histamine in the brains of mice [Sakai et al., Life Sciences, 48, 2397-2404(1991)]. This study also demonstrated that thioperamide did not affect the turnover rate of noradrenaline, dopamine, or serotonin in the brains of mice, which indicates that thioperamide is a good pharmacological tool for accelerating the release of neuronal histamine in the brain.[1]References
- The behavioral and biochemical effects of thioperamide, a histamine H3-receptor antagonist, in a light/dark test measuring anxiety in mice. Imaizumi, M., Onodera, K. Life Sci. (1993) [Pubmed]
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