NMDA Blockade Supresses L-dopa Induced Dyskinesias

Abstract

Parkinson's disease is the second leading neurological disease in the world and is caused by the death of dopaminergic neurons in the substantia nigra. L-dopa provides the most successful drug therapy, yet unfortunately, leads to abnormal involuntary movements known as dyskinesias. To cope with the loss of dopamine modulation from the substantia nigra, the NMDA receptors, a glutamate receptor subtype, increase activity in the striatum. It has been suggested that this hyperactivity of NMDA receptors contributes to the development of dyskinesias. Rats were unilaterally lesioned with 6OHDA and treated with L-dopa to simulate clinical conditions. Rats were also injected with felbamate, a NMDA antagonist that binds at the glycine site. This data was compared to parkinsonian rats injected with MK-801, another NMDA antagonists that binds within the ion channel, and vehicle-injected controls. Our results suggest that an NMDA blockade may repress dyskinesias and may offer an effective therapeutic approach to L-dopa induced dyskinesias.