Unilateral horizontal semicircular canal occlusion induces serotonin increase in medial vestibular nuclei: a study using microdialysis in vivo coupled with HPLC–ECD

Abstract

Unilateral single semicircular canal occlusion (USSCO) is an effective treatment for some cases of intractable vertigo. All patients suffer behavioural imbalance caused by surgery, and then recover with a resumption of vestibular function. However, the compensation mechanism has not been fully evaluated. Findings suggest that serotonin (5-HT) is released from nerve terminals, and plays a vital role in the plasticity of the central nervous system. In this study, we performed surgery of unilateral single semicircular canal occlusion (USSCO) on guinea pigs, and investigated the change of 5-HT by in vivo microdialysis of the medial vestibular nucleus (MVN) coupled with high-performance liquid chromatography and electrochemical detection (HPLC-ECD). A total of 12 guinea pigs were divided randomly into two groups, namely the USSCO group and the control group. Animals in the USSCO group underwent surgery of lateral horizontal semicircular canal occlusion, and those in the control group experienced the same operation but just to expose the horizontal semicircular canal without occlusion. Vestibular disturbance symptoms were observed in the case of the USSCO group, e.g. head tilting, and forced circular movements and spontaneous nystagmus at postoperative days 1 and 3. The basal level of 5-HT was determined to be 316.78 ± 16.62 nM. It elevated to 448.85 ± 24.56 nM at one day following occlusion (P = 0.001). The increase was completely abolished with the vestibular dysfunction recovery. The results showed that unilateral horizontal semicircular canal occlusion could increase the 5-HT level in MVN. 5-HT may play a significant role in the process of central vestibular compensation with residual vestibular function.

Effect of Fluoxetine and Acacetin on Central Vestibular Compensation in an Animal Model of Unilateral Peripheral Vestibulopathy

“…Some data show that gravitational [ 34 ] and caloric vestibular stimulations [ 35 ] are followed by an increased serotoninergic neurotransmission. Other studies attest to an increase in VN serotonin concentration after unilateral labyrinthectomy [ 36 ] or unilateral horizontal semi-circular canal occlusion [ 37 ]. Consistent with these data, if TTA is thought to cause an increase in VN serotonin levels, this could explain the fact that Fluoxetine treatment disrupts the vestibular syndrome, since this treatment is supposed to raise serotonin levels.…”

Drug–Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications

“…This category includes ondansetron (the most used), granisetron, tropisetron, dolasetron, and palonosetron (second generation antagonist) [ 40 ]. In an experimental model by Zhang et al, serotonin had an important role in vestibular compensation: the increase of its levels was documented after semi-circular canal occlusion [ 241 ]. Ondansetron showed a better effect in the control of nausea and vomiting, but a minor efficacy in the treatment of peripheral vertigo in comparison with promethazine [ 238 ].…”

In Vivo Recording of Ascorbate and Neural Excitability in Medial Vestibular Nucleus and Hippocampus Following Ice Water Vestibular Stimulation in Rats

“…According to the previous reports and our studies, vestibular compensation is followed with vertigo related to the long‐term change of the incoming signals from hippocampus, entorhinal cortex and vestibular cortex . In addition, medial vestibular nuclei (MVN) and primary somatosensory area are also involved in the vertigo procedure . Researchers have shown that hippocampal place cells could respond to vestibular stimulation, and vestibular stimulation could also affect neuronal cell proliferation in hippocampus .…”