Effects Of Dopamine D1 Receptor Agonist On The Electrical Activity Of Globus Pallidum In Rats With Parkinson’s Disease

Background: Parkinson’s disease(PD)is a common progressive neurodegenerative disease in middle-aged and elderly people,which is caused by the degeneration of dopaminergic neurons in the substantia nigra.Globus pallidus external segment(GPe)and globus pallidus internal segment(GPi)are important nuclei of direct and indirect pathways in basal ganglia circuits.SKF38393 is a common dopamine D1 receptor agonist that partially compensates for the lack of dopamine.Aims and significance: this study mainly studied the effects of dopamine D1 receptor agonist SKF38393 on behavior and GPe and GPi electrical activities in PD rats.Through the experimental study,we preliminarily determined whether dopamine receptor agonists could affect the behavior and electrophysiology of PD rats,providing a new idea for the research and treatment of PD.Research contents: 1.The optimal dose and the optimal time of D1 agonist SKF38393 were selected through behavioral experiments.2.To study the correlation between the action potential and the local field potential of two nuclei in PD rats after drug injection.Methods: PD model rats were established by unilateral brain injection of 6-OHDA method,and the self-made multi-channel electrodes were implanted into the target nuclear mass and and the catheter was embedded in the brain.The Plexon signal acquisition system was used to collect the electrical signals of the awake,static and continuous motion rats.The collected electrical signals were imported into Offline Sorter,Neuro Explorer and other software for cluster analysis and action potential change analysis.Then the field electricity of GPe and GPi was imported into Matlab for correlation analysis.Results:1.Screening results of D1 receptor agonist SKF38393After behavioral screening,it was found that after SKF38393 1.0 μg/side in the brain core striatum,all the indicators of normal and PD rats changed significantly within 20-50 min.The walking frequency of rats in the normal and PD groups increased significantly within 20-50 min.The indexes of Latency to fall also showed the same regularity: after drug injection,the time of normal and PD rats increased within 20-50 min.After drug injection,the number of mistakes in PD rats also decreased significantly within 20-30 min.In summary,the optimal dose of D1 receptor agonist SKF38393 is 1.0 μg/side,and the best action time is 20-50 min.2.GPe action potential change resultsGPe nuclei can be divided into two types of neurons: HFP and LFB.In the state of wakefulness,stillness and continuous movement,compared with the normal control group,the firing rate(spike/s)of the HFP neurons in the PD injured group was reduced.After SKF38393 drug injection,the firing rate had a significant recovery.CV value of HFP neurons increased in PD rats.After the injection of SKF38393,the resting state of CV value of PD rats was increased,and the change of movement state was not obvious.The firing rate of LFB neurons decreased in PD rats.After SKF38393 injection,the firing rate of LFB neurons in PD rats increased.CV value of LFB neurons increased in PD rats.After the injection of SKF38393,the resting state of LFB neuron CV value in PD rats was not significantly changed,and the motor state was increased.There was no significant change before and after drug treatment in normal rats’ GPe nuclei.3.GPi action potential change resultsGPi nuclei are classified as having only one class of neurons.Compared with the normal control group,the GPi neuron firing rate and CV value of the rats in the PD injury group increased when the rats were awake,still and in continuous motion.After the drug injection of SKF38393,the firing rate of GPi neurons in PD rats was significantly reduced under the conditions of waking,resting and continuous movement,CV goes up.However,before and after the drug injection in normal rats,the overall change of GPi neuron firing rate and CV value was not significant,and the CV value increased only in the exercise state.4.Correlation results of GPe-GPi in rats after drug injectionAfter PD injury,the correlation and synchronicity of GPe-GPi neurons in rats increased in the frequency range of 0.5-12 Hz.In 0.5-12 Hz and Beta(12-35 Hz),the average vector length of GPe-GPi neurons increased and the average phase orientation Angle decreased.In the continuous motion condition,the correlation value was not changed in the range of 0.5-35 Hz,and the average vector length value was increased.When GPe was used as a reference,the average phase orientation Angle of GPi neurons increased significantly in the range of 0.5-12 Hz,but other frequency band inside change was not significant.After drug injection with dopamine D1 receptor agonist SKF38393,the electric correlation changes of GPe and GPi field potential were not obvious.Conclusions: After the drug injection of SKF38393,the behavioral performance of PD rats was alleviated to a certain extent,which played a certain role in treatment renting.In terms of electrophysiology,the discharge rate of GPe and GPi neurons increased,and the discharge rate of GPi neurons decreased.However,no significant changes were observed in normal rats after drug injection.The electric correlation of GPe and GPi was significantly changed in the frequency band of 0.5-12 and 12-35 Hz,and the electric correlation was changed with no obvious regularity after drug injection.These results suggest that SKF38393 plays a role in direct and indirect pathways downstream of striatum after injection.