Objective: To characterize the patterns of cortico-basal ganglia oscillations induced by D1 or D2 receptor agonists in a rat model of L-DOPA-induced dyskinesia.

Background: In Parkinson’s disease (PD), dopamine replacement therapy with L-DOPA is complicated by development of abnormal involuntary movements (AIMs) termed L-DOPA-induced dyskinesia (LID). Studies in a rat model of LID have shown that the expression of AIMs coincides with the appearance of narrowband gamma oscillations (~80 Hz) in the motor cortex and other nodes of the cortico-basal ganglia network. Interestingly, a similar phenomenon has been described in dyskinetic PD patients. In addition, alterations in the spectral contents of other frequency bands have been reported after dopamine replacement therapy, including slow oscillatory activities in deep basal ganglia nuclei in dyskinetic subjects. To characterize the cortico-basal ganglia oscillations induced by D1 or D2 receptor agonists, large-scale recordings were performed in a rat model of LID.

Method: Unilaterally 6-OHDA-lesioned rats were primed with L-DOPA and then chronically implanted with microwire electrodes in motor-premotor cortices, striatum, globus pallidus and substantia nigra pars reticulata (SNr). Local field potential (LFP) and spike signals were recorded on consecutive sessions following treatment with L-DOPA or selective agonists of D1 and D2 receptors (SKF82958 and sumanirole, respectively) at doses inducing AIMs. Animals were freely moving to allow on-line AIM ratings, while overall motor activity was quantified using head-mounted accelerometers.

Results: Narrowband gamma activity was detected in all recorded structures following the administration of both D1 and D2 receptor agonists although with notable differences in amplitude and frequency. Compared to L-DOPA, D1- and D2-mediated dyskinesias were associated with opposite changes in the power of cortico-striatal 80 Hz oscillations (higher on D1, lower on D2 stimulation). There was a correlation between AIM scores and 80 Hz power, stronger after the administration of SKF82958 vs. L-DOPA and sumanirole. The power of theta (6-10 Hz) oscillations in the SNr increased specifically after treatment with sumanirole.

Conclusion: The findings so far show that dyskinesias mediated by D1 vs. D2 receptors are associated with different patterns of LFP oscillations in the cortico-basal ganglia network, suggesting distinct underlying circuit dysfunctions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/distinct-oscillatory-fingerprints-in-dyskinesias-mediated-by-d1-versus-d2-receptors/