The NMDA antagonists MK801 and CPP disrupt compensation for unilateral labyrinthectomy in the guinea pig.

Unilateral labyrinthectomy results in eye movement and postural disorders which diminish over time in a process of behavioral recovery called vestibular compensation. This compensation process is due to CNS plasticity which generates a renewal of spontaneous activity in vestibular nucleus neurons ipsilateral to the labyrinthectomy. However, the mechanisms responsible for the induction and maintenance of this neural recovery are unknown. The present results show that i.p. injections of the N-methyl-D-aspartate (NMDA) receptor antagonists MK801 [( (+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]-cyclohepten-5,10-imine maleate]) and CPP (3-[+/- )-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) disrupt the maintenance of compensation following unilateral labyrinthectomy, producing a reappearance of eye movement symptoms after compensation has been attained. These results suggest that NMDA receptors may be involved in the maintenance of the neural changes responsible for vestibular compensation.