Effects of histamine on 5-hydroxytryptaminergic neuronal activity in the rat hypothalamus.

Effects of pharmacological manipulations which mimic or enhance histaminergic neuronal transmission were determined on the activity of 5-hydroxytryptaminergic neurons projecting to the hypothalamus of male rats. Intracerebroventricular administration of histamine decreased 5-hydroxytryptamine (5-HT) and increased 5-hydroxyindoleacetic acid (5-HIAA) concentrations in several hypothalamic nuclei; these effects were blocked by the histamine H1 receptor antagonist mepyramine but not the histamine H2 receptor antagonist zolantidine. Blockade of the 5-HT reuptake system by fluoxetine did not prevent histamine-induced decreases in 5-HT concentrations suggesting that histamine is not transported into nerve terminals via the 5-HT reuptake system to subsequently displace 5-HT stores. These data suggest that exogenous histamine increases 5-hydroxytryptaminergic neuronal activity through an action at histamine H1 receptors. In contrast, neither the histamine H3 receptor antagonist thioperamide, the histamine-N-methyltransferase inhibitor metoprine, nor combined thioperamide-metoprine treatment affected concentrations of 5-HT or 5-HIAA suggesting these agents, which purportedly enhance endogenous histaminergic transmission, do not affect 5-hydroxytryptaminergic neuronal activity. These results reveal that procedures commonly employed to study central actions of histamine differentially affect 5-hydroxytryptaminergic neuronal activity in the rat hypothalamus.