Previous studies have shown an excitatory effect of histamine on neurons in two cerebellar nuclei, the fastigial nucleus and the interposed nucleus. Here we investigated action of histamine on the dentate nucleus (DN), another nucleus of the cerebellum, and provided more evidence for motor control by histamine via the cerebellum. Spontaneous unitary discharge of neurons in the DN was extracellularly recorded by use of cerebellar slice preparations. In total 79-recorded neurons, which were from 53 cerebellar slices, 67 neurons (84.8%) had an excitatory response to histamine stimulation, and the rest (15.2%) were not reactive. The histamine-induced excitation of the DN neurons was not blocked by low-Ca(2+)/high-Mg(2+) medium, demonstrating that this effect of histamine was postsynaptic. Triprolidine, an antagonist of histamine H(1) receptors, did not block the excitatory effect of histamine, but ranitidine, an antagonist for H(2) receptors, blocked the excitatory response to histamine in a concentration-dependent manner. Further, histamine H(1) receptor agonist 2-pyridylethylamine did not elicit any response of DN neurons, but H(2) receptor agonist dimaprit had an excitatory action on the DN cells and this action was blocked by ranitidine. These results indicate that histamine excites cerebellar DN neurons via histamine H(2) receptors. Since the DN receives hypothalamocerebellar histaminergic projections and plays a role in initiation and planning of somatic movement, the postsynaptic excitation of the DN neurons by histamine suggests the possibility that the initiation and planning of movement may be modulated by the histaminergic projections.