Histamine excites neurons of the inferior vestibular nucleus in rats by activation of H1 and H2 receptors.

By using brain slice preparations and extracellular recordings, the effect of histamine on spontaneous firing activities of neurons in the inferior vestibular nucleus (IVN), a key structure responsible for integration of vestibular, multisensory, and cerebellar inputs, in rats was investigated. Perfusing slices with histamine (1-10μM) elicited an excitatory response on IVN neurons. The responses were not blocked by low Ca(2+)/high Mg(2+) medium, indicating a direct postsynaptic effect of the amine. Furthermore, the histamine-induced excitation was partially blocked by selective histamine H1 receptor antagonist mepyramine (1μM) and H2 receptor antagonist ranitidine (1μM), respectively. Co-application of mepyramine and ranitidine nearly totally antagonized the histamine-induced excitation. Additionally, both selective H1 receptor agonist 2-pyridylethylamine (30-300μM) and H2 receptor agonist dimaprit (10-100μM) effectively mimicked the excitatory action of histamine on IVN neurons. Moreover, selective H4 antagonist JNJ7777120 (10μM) and agonist VUF8430 (30-300μM) had no effect on IVN neurons. These results demonstrate that histamine excites IVN neurons via postsynaptic H1 and H2 rather than H4 receptors, and suggest that the central histaminergic system actively modulate all four major vestibular nuclei including the IVN and may subsequently influence the vestibular nuclei-related reflexes and functions.