Abstract: In the vestibular nuclei, acute hypotension induces excitation of electrical activity and expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK). Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. We investigated the signaling pathway of glutamate and its receptors in the vestibular nuclei following acute hypotension in conscious rats. Glutamate release and the expression of c-Fos protein in the medial vestibular nuclei (MVN) were measured by microdialysis and immunohistochemical analysis, respectively. We compared the responses of rats with unilateral labyrinthectomy to unaltered controls. Acute hypotension was induced by infusing sodium nitroprusside (SNP) into the femoral vein. In the control group, glutamate release and the expression of c-Fos protein increased in the bilateral MVN following acute hypotension. In the unilateral labyrinthectomy group, glutamate release and the expression of c-Fos protein increased in the MVN contralateral to the lesion, but did not change in the ipsilateral MVN following acute hypotension. Microinjection of NMDA or AMPA into the lateral ventricle increased the expression of c-Fos protein in the bilateral MVN of conscious intact labyrinthine rats. However, after intracerebroventricular microinjection of MK-801 or CNQX little c-Fos protein was expressed in the bilateral MVN of these rats following acute hypotension. These results suggest that in response to acute hypotension, excitatory afferent signals from the peripheral vestibular receptors release glutamate into postsynaptic neurons in the vestibular nuclei. These excitatory signals are transmitted through the NMDA receptors and AMPA receptors of glutamate in the vestibular system. [Copyright &y& Elsevier]