Regional Distribution of 5-HT 1A, 1B, and 1D Receptors in Rat Vestibular Nuclei (Vn) and Inner Ear

ABSTRACT

Migraine and anxiety disorders are frequently co-morbid with balance disorders. Potential mechanisms for migrainous vertigo include sites of action of 5-HT (serotonin) 1B and 1D receptor agonists such as rizatriptan, which attenuate motion sickness in migraineurs. Selective serotonin reuptake inhibitors (SSRIs) are also known to be efficacious in the treatment of vertigo. Relative distribution of the 5-HT receptor subtypes and their functional roles in the vestibular nuclei and inner ear is still unknown. Using 5-HT1A, 1B, AND 1D receptors-specific antibody, we have demonstrated a differential distribution of these receptor subtypes within the rat vestibular nuclei and inner ear. For 5-HT receptor subtypes expression in the vestibular and auditory periphery, most ganglion cells in the vestibular ganglion showed immunoreactivity for 5-HT1A, 5-HT1B and 5-HT1D receptors. In addition, 5-HT1B and 1D receptors immunopositive reactivities were associated with endothelial cells of small blood vessels in the vestibular ganglion and nerve, endothelial cells in both the spiral ligament deep to the spiral prominence and stria vascularis and endothelial cells on blood vessels along the margins of the spiral ganglion. For 5-HT receptor subtypes expression in the vestibular nuclei (VN), the 5-HT1A, 1B and 1D receptors were expressed differentially in the VN. Fine varicose axons in the periventricular plexus showed intense 5-HT1A receptor expression in the medial VN (MVN) and extended into the superior VN (SVN). By contrast, 5-HT1B receptors were not expressed the ventricular plexus axons. Rather, 5-HT1B and 1D receptors immunopositive cell bodies and neuronal processes were dense in rostral MVN, dorsal SVN, lateral VN (LVN) and ventral aspect of nucleus prepositus hypoglossi (NPH). In the present study, inner ear and vestibular nuclei showed distinct distributions of 5- HT1A, 1B and 1D receptors expressions that are parallel to their distribution in peripheral and central nociceptive pathways. These differentially distributed 5-HT receptor subtypes are potential targets to explain the efficacy of SSRIs and triptans in treating migraine and migrainous vertigo.