Role of NMDA receptors in the compensation of ocular nystagmus induced by hemilabyrinthectomy in the guinea pig.

The possibility that N-methyl-D-aspartate (NMDA) receptor activation plays a role in inducing the vestibular compensation following hemilabyrinthectomy (HL) in guinea pigs, was verified by means of continuous intraventricular osmotic pumping of DL-2-Amino-5-phosphono-valeric acid (APV). Our results show that high doses (40 and 20 mM) of APV decrease both the combined OKR and VOR and the nystagmus following HL. Low doses of APV (2.5 mM), affect the time course of the ocular compensation by maintaining a higher level of nystagmus beat frequency and by delaying the nystagmus disappearance. On the contrary, the compensation time course is not affected by administering APV later on in the compensation period. Therefore, it appears that NMDA receptors are activated during the precocious phase of vestibular compensation, when a large vestibular imbalance is present. This finding is explained by the development of NMDA receptor hypersensitivity, in the functionally inactivated commissural system or by the occurrence of NMDA-mediated long-term potentiation.