Colocalization of 5-HT1F receptor and glutamate in neurons of the vestibular nuclei in rats

Abstract

Interplay between migraine and balance disorder morbidities has been a topic of interest for many years. Serotonin (5-HT) receptor is closely related with migraine and is associated with vestibular symptoms. The mechanism underlying migrainous vertigo, however, has not been determined. 5-HT1F receptor has recently attracted attention in the treatment of migraine, and the release of glutamate from trigeminal neurons has been implicated in migraine. In this study, the authors observed the colocalization of 5-HT1F receptor and glutamate in the vestibular nuclei of rats using double immunofluorescence, which suggests that 5-HT1F receptor might modulate glutamate release from the vestibular nuclei. The results of this study suggest that 5-HT1F receptor agonists represent a potential therapeutic strategy for migraine and balance disorders by blocking the release of glutamate.

A possible explanation for dizziness following SSRI discontinuation

“…Since glutamate is the major excitatory neurotransmitter in the VNC and the neurotransmitter mediating input from the vestibular nerve [11], this suggests that the impact of changes in serotonin levels on VNC neurons could be dramatic. Consistent with this evidence, 5-HT1F receptors have recently been reported to be co-localized with glutamate in the VNC [14]. Ahn et al [14] suggested that the 5-HT1F receptor may modulate the release of glutamate from VNC neurons, which could potentially have a powerful effect on the transmission of information about balance and orientation to the rest of the brain.…”

“…Consistent with this evidence, 5-HT1F receptors have recently been reported to be co-localized with glutamate in the VNC [14]. Ahn et al [14] suggested that the 5-HT1F receptor may modulate the release of glutamate from VNC neurons, which could potentially have a powerful effect on the transmission of information about balance and orientation to the rest of the brain.…”

“…If 5-HT1F receptors and glutamate are co-localized on VNC neurons and activation of 5-HT1F receptors reduces glutamate release [14], then the decrease in serotonin may result in the reduced activation of the 5-HT1F receptors, thereby increasing glutamate release by VNC neurons. If this happened bilaterally, as would be expected with a systemically administered drug, then both the left and right VNCs would send increased vestibular signals to the rest of the brain.…”

“…Interestingly, approximately one-eighth of the serotonergic dorsal raphe neurons projecting to the VNC also project into the central amygdaloid nucleus [13], suggesting a surprising connection between the vestibular system and anxiety. VNC neurons express a number of different serotonergic receptor subtypes, including 5-HT1A, 5-HT1F, 5-HT2A and 5-HT3 receptors [11,14]. Electrophysiological studies have shown that serotonin has effects on the spontaneous firing rate of medial vestibular nucleus neurons via 5-HT1A and 5-HT2 receptors [11].…”

Neurologic bases for comorbidity of balance disorders, anxiety disorders and migraine: neurotherapeutic implications

“…Immunoreactivity for 5-HT 2A [102], 5-HT 1B and 5-HT 1D receptors [103] are expressed fairly widely by vestibular nucleus neurons, but 5-HT 1A receptors in the vestibular nuclei are expressed heavily by ventricular plexus axons. More recently, it has been reported that 5-HT 1F receptors and glutamate immunoreactivity are colocalized extensively within the vestibular nuclei [104], with prominent staining in the lateral vestibular nucleus. These findings suggest that circuits for vestibular sensorimotor pathways receive regionally-specialized serotonergic inputs and include potential sites of action for triptans and selective serotonin reuptake inhibitors (SSRIs).…”