The effects of histamine on the firing of cerebellar granule cells were inv
estigated in vitro. Histamine predominantly produced excitatory (117/123, 9
5.1%) and in a few cases inhibitory (6/123, 4.9%) responses in granule cell
s. The histamine-induced excitation was not blocked by perfusing the slice
with low Ca2+/high Mg2+ medium, supporting a direct postsynaptic action of
histamine. The H-1 receptor antagonists triprolidine and chlorpheniramine s
ignificantly diminished the histamine-induced excitation, but the H-2 recep
tor antagonist ranitidine did not significantly reduce the excitation. On t
he other hand, the H-2 receptor agonist dimaprit could elicit a weak excita
tion of granule cells. This dimaprit-induced excitation was blocked by rani
tidine but not triprolidine. These results reveal that the excitatory effec
t of histamine on cerebellar granule cells is mediated by both H-1 and H-2
receptors with a predominant contribution of H-1 receptors. The relevance o
f these findings to the possible function of the hypothalamocerebellar hist
aminergic fibers in cerebellum is discussed. (C) Elsevier, Paris.