What is the Role of the NMDA Receptor in the Development of L-DOPA-induced dyskinesias?
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Parkinson?s Disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra. A common treatment for PD patients is levodopa (L-dopa). Unfortunately, long-term use of L-dopa is problematic, often resulting in the development of dyskinesias, the abnormal involuntary movements (AIMs) that manifest in the face and limbs. The NMDA receptor is an ionotropic receptor subtype for glutamate, a major excitatory neurotransmitter. Previous studies have shown that blocking this glutamate receptor may uncover mechanisms involved in the development of abnormal involuntary movements. MK-801 is one particular example of an NMDA receptor antagonist that easily crosses the blood brain barrier. In our study, we evaluated the effect of an NMDA-receptor blockade on the development of L-dopa induced dyskinesias.At this point, it is evident that an NMDA-receptor blockade is able to suppress the development of limb and axial dyskinesias, yet is ineffective in suppressing masticatory dyskinesias and rotational behavior. On the contrary, rotational behavior was promoted by MK-801 on the first day of observations. The inability of an NMDA receptor blockade to suppress masticatory dyskinesias suggests that other receptors are involved in their development. Such data suggests that glutamatergic drugs may be therapeutic for some AIMs categories but not all.This differential effect may have important clinical implications for treating humans with dykinesias.