The tonic discharge of 71 medial vestibular nucleus (MVN) neurones was recorded in slices of the dorsal brainstem of young adult rats. Bath application of
histamine caused a dose-related excitation in 59 of the 71 cells (83%), the remaining 12 (17%) being unresponsive.
Dimaprit, a selective
H2 agonist, also caused excitation in all 20 cells tested. The
histamine-induced excitation and the response to
dimaprit were antagonised by the selective H2 antagonist
ranitidine, confirming that the H2 subtype of
histamine receptor is involved in mediating the effects of
histamine on these cells.
Triprolidine, a selective H1 antagonist, also antagonised the excitation caused by
histamine, at a concentration (0.3 microM) which left the H2 receptor-mediated response to
dimaprit unchanged. Thus the excitatory effects of
histamine on MVN cells in the rat involve two components mediated through H1 and H2 receptor-linked mechanisms, respectively.
Betahistine, a weak
H1 agonist and H3 antagonist, had little excitatory action when applied on its own, but significantly reduced the excitation caused by
histamine when the two drugs were applied together. The effects of
betahistine were consistent with a partial-agonist action at
H1 receptors on MVN cells, reducing the excitatory responses to
histamine presumably by occupying these receptor sites in competition with the exogenously applied
neurotransmitter. This partial-agonist action of
betahistine may be an important part of its mechanism of action in the symptomatic treatment of
vertigo and
motion sickness, since it is likely to occur not only in the MVN but also in many brain regions, including the thalamus and cortex, which express
H1 receptors and which are innervated by the hypothalamic histaminergic system. Thus the effectiveness of
betahistine and other anti-H1 drugs against
motion sickness may be explained by their action in reducing the effects of the excess histamine release induced in such conditions in various brain areas, including the MVN.