Eltoprazine modulated gamma oscillations on ameliorating L‐dopa‐induced dyskinesia in rats

Background Levodopa-induced dyskinesia (LID) is a challenging complication in the advanced stages of Parkinson's disease (PD). Excessive beta and gamma oscillations of PD and LID have been frequently reported in recent cross-sectional studies. Objective We investigate the temporal features of beta and gamma activity during the development of PD and LID, as well as the regulatory role of dopamine I receptors (D1R) and dopamine III receptor (D3R). Methods We collected motor behavior and electrophysiological data during the development of PD and LID, after interventions with D1R and D3R antagonists and agonists. Results We demonstrated exaggerated beta-band activity in PD state and excessive gamma-band activity during on-state dyskinesia. Subsequently, process-dependent increased beta activity correlated with bradykinesia during PD modeling, while a process-dependent increased gamma activity correlated with dyskinesia under the cumulative effects of L-dopa during on-state dyskinesia. Finally, both D1R and D3R were found to be involved in regulating dyskinesia and gamma activity. Conclusion Dynamic oscillations is closely associated with motor behavior, and mapping dynamic oscillations should be related to optimizing DBS parameters and developing personalized neurotherapeutic targeting.

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Local field potentials and neural activity in motor networks in levodopa-induced dykinesia in a model of Parkinson’s disease

Brazhnik,

Mysin,

Novikov

2024

Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova

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Levodopa, a metabolic precursor of dopamine (DA), is used to treat movement disorders in Parkinson’s disease (PD). Long-term use of levodopa causes a serious side effect known as levodopa-induced dyskinesia (LID). With the development of LID, high-frequency gamma oscillations (80–120 Hz) are reported in recordings of local field potentials (LFPs) from the motor cortex (MCx) in rats with experimental PD and in patients with Parkinson’s disease. The mechanisms underlying the occurrence of these oscillations and their connection with LID are not entirely clear. The study of activity in divisions of the motor network can provide valuable information about the mechanisms of development of pathological gamma-oscillations and LID. Rats with experimental PD were treated with levodopa for 7 days. Local field potentials and neural activity were recorded from electrodes implanted in the motor cortex, ventromedial nucleus of the thalamus (Vm), and substantia nigra pars reticularis (SNpr). Dyskinesia was assessed using a standard abnormal involuntary movement scale. Administration of levodopa significantly reduced the power of beta-oscillations (30–36 Hz) in all 3 parts of the motor neural network associated with bradykinesia in PD and caused the appearance in Vm and MCx coherent LFP oscillations in the high gamma-frequency range. Their coherence increased during priming between days 1 and 7. This activity was strongly associated with the occurrence of dyskinesia. In LID, an increase in the frequency of neuronal activity in Vm and MCx was accompanied by increased synchronization of neuronal activity with cortical gamma-oscillations in VM (68%) and MCx (25%). In contrast to Vm and MCx, SNpr did not exhibit gamma-range oscillatory activity during LID, and its neural activity was not synchronized with LFPs in Vm or MCx. It is significant that during the LID period the frequency of SNpr spike activity in most recordings (76%) decreased significantly and was approximately three times lower than the initial one (before the administration of levodopa). Administration of the antidyskinetic drug, 8-OH-DPAT, restored the initial characteristics of LFPs (30–36 Hz oscillation), neuronal activity, and bradykinesia. Thus, repeated administration of levodopa leads to a decrease of the inhibitory control in motor neural networks due to a significant reduction in activity of SNpr. Obviously, Vm and SNpr can be considered as the most important components of the motor neural network, making the main contribution to the occurrence of high-frequency gamma oscillations and LID.

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Eltoprazine modulated gamma oscillations on ameliorating L‐dopa‐induced dyskinesia in rats

Cited by 4 publications

References 45 publications

Fenobam modulates distinct electrophysiological mechanisms for regulating excessive gamma oscillations in the striatum of dyskinetic rats

Fenobam modulates distinct electrophysiological mechanisms for regulating excessive gamma oscillations in the striatum of dyskinetic rats

RETRACTED: Temporal features of gamma activity in STN mediated by dopamine receptors in dyskinetic rat

Local field potentials and neural activity in motor networks in levodopa-induced dykinesia in a model of Parkinson’s disease

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