Excitatory effects of histamine on cerebellar interpositus nuclear cells of rats through H(2) receptors in vitro.

Neuroanatomical studies have revealed a direct hypothalamocerebellar histaminergic pathway, and our previous studies have demonstrated an excitatory effect of histamine on granule and Purkinje cells of the cerebellar cortex. In this study, we further investigated the effect of histamine on the neuronal firing of cerebellar interpositus nucleus (IN) by using cerebellar slice preparations. Eighty-seven IN cells were recorded from 38 slices. The vast majority of the cells responded to histamine stimulation with an excitatory response (79/87, 90.8%), and the rest of them showed no reaction (8/87, 9.2%). The histamine-induced excitation was not blocked by application of low-Ca(2+)/high-Mg(2+) medium (n=8), supporting a direct postsynaptic action of histamine. The histamine H(2) receptor antagonist ranitidine effectively blocked the excitatory response of IN cells to histamine (n=23), but the histamine H(1) receptor antagonist triprolidine could not significantly block the histamine-induced excitation, or only very slightly decreased the excitatory effect of histamine on the cells (n=21). On the other hand, the highly selective histamine H(2) receptor agonist dimaprit mimicked the excitatory effect of histamine on IN cells and the dimaprit-induced excitation was also blocked by ranitidine (n=14). Successively perfusing slices with the medium containing ranitidine and triprolidine, respectively, we found that ranitidine exhibited the same blocking effect on the dimaprit-induced excitation, but triprolidine had no such effect (n=8). Moreover, the histamine H(1) receptor agonist 2-pyridylethylamine did not show any effect on the IN cells (n=9). These results demonstrate that histamine excites cerebellar IN cells via the histamine H(2) receptor mechanism. Together with our previous results, we suggest that the hypothalamocerebellar histaminergic fibers may modulate neuronal activities of the cerebellar cortex and deep nuclei in parallel. The significance of the excitatory effect of histamine on the cerebellar nuclear cells is discussed. Copyright 2002 Elsevier Science B.V.