The NMDA receptor antagonist CGS 19755 disrupts recovery following cerebellar lesions.

PURPOSE: To test whether activation of NMDA receptors is required for the maintenance of the posture and motor behavior recovered from cerebellar lesions, an NMDA antagonist (CGS 19755) was systemically administered to totally or partially cerebellectomized rats. METHODS: Three groups of animals were tested: rats that had undergone a total cerebellectomy four months before drug administration; rats that had undergone a right hemicerebellectomy four months before drug administration; intact control animals. RESULTS: Under drug action in the control animals the postural pattern was slightly influenced, showing a light worsening, and motor skills requiring coordinated motor performance and subtle balance control were markedly worsened. Conversely, in the lesioned groups the cerebellar symptomatology dramatically worsened, and both groups of animals looked like they had just been operated, exhibiting the whole repertoire of postural and motor behaviors of cerebellar origin. In particular, limb hyperflexion, wide-based locomotion and the tendency to side falls were prevalent in the cerebellectomized animals, while tremor and body tilt were prevalent in the hemicerebellectomized group. CONCLUSION: The reappearance of severe postural and motor symptomatology has to be interpreted as a "decompensation" evoked by the NMDA-receptor antagonist, suggesting the involvement of NMDA receptors in the maintenance of compensation of disturbances of cerebellar origin.