Plasticity of histamine H(3 )receptor expression and binding in the vestibular nuclei after labyrinthectomy in rat

BACKGROUND: 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(3 )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(1 )receptor agonist and an H(3 )receptor antagonist, can accelerate the process of vestibular compensation. RESULTS: Expression levels for histamine H(3 )receptor (total) as well as three isoforms which display variable lengths of the third intracellular loop of the receptor were analyzed using in situ hybridization on brain sections containing the rat medial vestibular nucleus after unilateral labyrinthectomy. We compared these expression levels to H(3 )receptor binding densities. Total H(3 )receptor mRNA levels (detected by oligo probe H(3X)) as well as mRNA levels of the three receptor isoforms studied (detected by oligo probes H(3A), H(3B), and H(3C)) showed a pattern of increase, which was bilaterally significant at 24 h post-lesion for both H(3X )and H(3C), followed by significant bilateral decreases in medial vestibular nuclei occurring 48 h (H(3X )and H(3B)) and 1 week post-lesion (H(3A), H(3B), and H(3C)). Expression levels of H(3B )was an exception to the forementioned pattern with significant decreases already detected at 24 h post-lesion. Coinciding with the decreasing trends in H(3 )receptor mRNA levels was an observed increase in H(3 )receptor binding densities occurring in the ipsilateral medial vestibular nuclei 48 h post-lesion. CONCLUSION: 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(3) receptor may be an essential part of pre-synaptic mechanisms required for reestablishing resting activities 48 h after unilateral labyrinthectomy.