Dutia M.B. Betahistine, 6estibular function and compensation: in 6itro studies of 6estibular function and plasticity. Acta Otolaryngol 2000; Suppl 544: 11-14.Histamine has an excitatory action on rat medial vestibular nucleus neurones in 6itro, an effect that is mediated by histamine H 1 and H 2 receptors. Betahistine, which is a weak agonist at the H 1 receptor and a moderate antagonist at the presynaptic H 3 autoreceptor, weakly excites medial vestibular nucleus cells but antagonizes their responses to histamine. Experiments were carried out on rat medial vestibular nucleus cells in 6itro using slices prepared from animals that had undergone unilateral labyrinthectomy (UL). There was a significant increase in the intrinsic excitability of medial vestibular nucleus cells in the rostral region of the ipsi-lesional nucleus within 4 h post-UL, which was sustained for the following week. These changes in intrinsic excitability of the medial vestibular nucleus neurones were abolished in animals that were not exposed to the secretion of stress hormones that normally occurs following UL. Histamine is also released in response to the stress associated with vestibular dysfunction. It is possible that the beneficial effects of betahistine on vestibular compensation are related to an interaction between histaminergic receptors activated by the parallel release of histamine and the activation of glucocorticoid receptors through the activation of the stress axis. Further study of the interactions between histamine receptors and the activation of the stress axis may be useful in understanding the effects of betahistine on vestibular plasticity.

Extracellular and whole-cell patch clamp intracellular recordings were made from rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to selective mu-, kappa- and delta-opioid receptor agonists and antagonists were examined. Of 127 neurones tested, the large majority were inhibited in a dose-dependent manner by the delta-opioid receptor agonists [D-Ala2, D-Leu5]-enkephalin (DADLE) and [D-Pen2, Pen5]-enkephalin (DPLPE). The mu-opioid receptor agonist morphine and the kappa-receptor agonist U50,488 did not affect the tonic discharge rate of any of the 63 MVN cells tested. The delta-receptor antagonist naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE. Weak excitatory responses to high doses of DADLE were seen in only two MVN cells. These results demonstrate the presence of delta- but not mu- or kappa-opioid receptors on tonically active MVN neurones. Whole-cell intracellular recordings from MVN cells in a current clamp showed that the DADLE-induced inhibition was accompanied by membrane hyperpolarisation and decrease in input resistance, while voltage clamp experiments showed that DADLE induced an outward membrane current that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of outward K currents, in a similar way to the effects of opioids in other areas of brain. The inhibitory effects of DADLE increased linearly with age, so that the responses to DADLE in the youngest animals used here (60-80 g, approx. 3 weeks of age) were relatively small, increasing significantly over the following 2-3 weeks. This age-dependence may be due to post-natal changes in the density of delta-opiate receptors or the efficacy of the signalling pathways activated by them in the MVN cells over this time.