Role of the vestibular nuclei in endothelin-1-induced barrel rotation in rats.

The fourth or lateral ventricular injection of endothelin-1 resulted in a dose-dependent increase in the barrel rotation and produced marked induction of c-Fos-positive cells in the vestibular nuclei. The doses of the former injection were lower and had shorter mean latent periods compared with the later injection. c-Fos expression after endothelin-1 injection was prevented by the pretreatment with the endothelin ET(A) receptor antagonist, cyclo(D-alpha-aspartyl-L-propyl-D-valyl-L-leucyl-D-tryptophyl) (BQ-123), the glutamate NMDA receptor antagonist, dizocilpine maleate (MK-801), or the L-type Ca(2+) channel antagonist, verapamil, in addition to the incidence of the rotational behavior. There was a significant difference in c-Fos expression between the right and left medial vestibular nuclei, and the number of c-Fos-labeled neurons in the medial vestibular nucleus was markedly increased on the opposite side of the rotational direction. These results suggest that the elicitation of the barrel rotation may be mediated by endothelin ET(A) receptors, glutamate NMDA receptors, and L-type Ca(2+) channels. The changes in the receptor and channel systems induced by endothelin-1 injections appeared to exert crucial influences on the vestibular nuclei and then on the maintenance of equilibrium. The direction of the barrel rotation has a deep connection with the imbalance of neuronal activity in the left and right medial vestibular nuclei.