| Summary: | <p>Abstract</p> <p>Background</p> <p>In rat, deafferentation of one labyrinth (unilateral labyrinthectomy) results in a characteristic syndrome of ocular and motor postural disorders (e.g., barrel rotation, circling behavior, and spontaneous nystagmus). Behavioral recovery (e.g., diminished symptoms), encompassing 1 week after unilateral labyrinthectomy, has been termed vestibular compensation. Evidence suggesting that the histamine H<sub>3 </sub>receptor plays a key role in vestibular compensation comes from studies indicating that betahistine, a histamine-like drug that acts as both a partial histamine H<sub>1 </sub>receptor agonist and an H<sub>3 </sub>receptor antagonist, can accelerate the process of vestibular compensation.</p> <p>Results</p> <p>Expression levels for histamine H<sub>3 </sub>receptor (total) as well as three isoforms which display variable lengths of the third intracellular loop of the receptor were analyzed using <it>in situ </it>hybridization on brain sections containing the rat medial vestibular nucleus after unilateral labyrinthectomy. We compared these expression levels to H<sub>3 </sub>receptor binding densities.</p> <p>Total H<sub>3 </sub>receptor mRNA levels (detected by oligo probe H<sub>3X</sub>) as well as mRNA levels of the three receptor isoforms studied (detected by oligo probes H<sub>3A</sub>, H<sub>3B</sub>, and H<sub>3C</sub>) showed a pattern of increase, which was bilaterally significant at 24 h post-lesion for both H<sub>3X </sub>and H<sub>3C</sub>, followed by significant bilateral decreases in medial vestibular nuclei occurring 48 h (H<sub>3X </sub>and H<sub>3B</sub>) and 1 week post-lesion (H<sub>3A</sub>, H<sub>3B</sub>, and H<sub>3C</sub>). Expression levels of H<sub>3B </sub>was an exception to the forementioned pattern with significant decreases already detected at 24 h post-lesion. Coinciding with the decreasing trends in H<sub>3 </sub>receptor mRNA levels was an observed increase in H<sub>3 </sub>receptor binding densities occurring in the ipsilateral medial vestibular nuclei 48 h post-lesion.</p> <p>Conclusion</p> <p>Progressive recovery of the resting discharge of the deafferentated medial vestibular nuclei neurons results in functional restoration of the static postural and occulomotor deficits, usually occurring within a time frame of 48 hours in rats. Our data suggests that the H<sub>3</sub> receptor may be an essential part of pre-synaptic mechanisms required for reestablishing resting activities 48 h after unilateral labyrinthectomy.</p>
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