Roles of glutamate receptor subtypes in the development of vestibular compensation after unilateral labyrinthectomy in the guinea pig

We investigated the roles of ionotropic glutamate receptor subtypes in the development and recovery of spontaneous nystagmus (SN) after unilateral labyrinthectomy (UL) in guinea pigs. When administered at 3 h after UL, N-methyl-D-aspartate (NMDA) and kainate (KA),which are NMDA and non-NMDA receptor agonists, respectively, increased the frequency of SN. The effect of KA was more potent than that of NMDA. in contrast to these agonists, MK-801 and CNQX decreased the frequency of SN. Although the administration of KA at 48 h after UL increased the frequency of SN, it did not exhibit any effects at 72 h after UL. MK-801 caused a recurrence of SN following administration at 48 and 72 h after UL. Neither NMDA nor CNQX exhibited any effects after administration at 48 or 72 h after UL. A newly synthesized compound, NC-1200, which has inhibitory action on the glutamate response, decreased the frequency of SN in a dose-dependent manner following administration at 3 h after UL, but did not exhibit any effects when administered at 48 and 72 h after UL. From these results, it was found that NMDA and non-NMDA receptors play important roles in the development of SN after UL, and that the NMDA receptor contributes to the development of ocular motor compensation. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.