Is monoamine turnover in the brain regulated by histamine H₃ receptors?

To clarify whether monoamine neuron activity in the brain is regulated by histamine H₃ receptors, the effects of a potent and seletive H₃ agonist, (R) α-methylhistamine and an antagonist, thioperamide, on monoamine metabolism were examined in the telecephalon, hypothalamus and brainstem of the rat and the whole brain . Histamine turnover estimated from the pargyline-induced tele-methylhistamine accumulation decreased markedly with (R) α-methylhistamine administration (6.3 mg/kg i.p.) and increased with thioperamide administration (5 mg/kg i.p.) in all the brain regions examined. (R) α-Methylhistamine and thioperamide, at the doses tested, neither induced any significant changes in the levels of noradrenaline or 3,4-dihydroxyphenylacetic acid nor had any significant influence on the α-methyl-p-tyrosine-induced declines of the noradrenaline and dopamine levels in all the brain regions examined. However, thioperamide significantly decreased the dopamine level only in the rat telencephalon. In general, thioperamide increased 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratios and pargyline-induced 5-HT accumulation. However, (R) α-methylhistamine affected neither the 5-HT nor the 5-HIAA level. The pargyline-induced 5-HT accumulation was slightly enhanced by (R) α-methylhistamine in the whole mouse brain. The enhancement by thioperamide of pargyline-induced 5-HT accumulation was not inhibited by (R) α-methylhistamine. These results suggest that H₃ receptors have no important roles in the regulation of monoaminergic activity in contrast with their regulatory function in histaminergic activity. In addition, thioperamide at high doses may enhance 5-HT turnover independently of H₃ receptors.