| Background: Parkinson’s disease is caused by the degeneration and loss of dopaminergic neurons in the substantia nigra.The substantia nigra-striatum pathway has an impairment of information transmission,resulting in a number of symptoms,including static tremor,limb muscle rigidity,postural balance problems,slow movement and other problems.The globus pallidus can regulate the movement of the body,which is divided into globus pallidal external segments and globus pallidal internal segments.Some movement disorders caused by PD are closely related to the abnormal discharge of the globus pallidus.Therefore,some movement disorders of PD can be improved by changing the discharge of the neurons in the globus pallidus.Dopamine D2 receptor can mediate the indirect pathway of basal ganglia and deliver inhibitory neurotransmitters to the globus pallidal external segments to express D2 receptor.Some symptoms of Parkinson’s disease can be alleviated by increasing the expression of the D2 receptor.In recent years,dopamine receptor agonists have attracted high attention,dopamine agonists can imitate dopamine to stimulate dopamine receptors,reduce the abnormal of globus pallidus in basal ganglia loop excitability.Quinpirole is a kind of dopamine D2 receptor agonists,it can selectively bind to the D2 receptor,so the dopamine D2 receptor agonist quinpirole is a kind of treatment options.Objective: 1、To research the effect of quinpirole,a dopamine D2 receptor agonist,on the behavior of rats with Parkinson’s disease,and to screen out the effective dose and optimal action time of quinpirole.2、To study the effects of dopamine receptor agonists on the electrophysiology of globus pallidus in Parkinson’s disease rats.Methods: Firstly,a Parkinson’s rat model was established by unilateral injection of 6-hydroxydopamine(6-OHDA).Then,the rats were divided into control group,PD group,control+quinpirole,PD+quinporole.1、The self-made treadmill was used in the laboratory and the appropriate rotation speed was selected to make the rats exercise on the treadmill.Using the behavioral indicators: Latency to fall and Steps,the optimal dose and duration of quinpirole were determined,and whether quinpirole could improve the movement disorders of rats with Parkinson’s disease was observed.2、The administration catheter was inserted into the dorsolateral striatum of rats,the laboratory’s homemade 16 channel nickel-chromium alloy electrodes were implanted into the rat globus pallidus,the use of signal acquisition system to collect and analyze the normal group and PD rats quinpirole drugs before and after the intervention of action potential,and Local field potentials(the Local field potential,LFP)change and GPe,GPI correlation analysis of two nuclei.Results:1.Quantitative evaluation of the dopamine D2 agonist quinpirole behavioral experimentIn conclusion,the effective dose of dopamine D2 agonist quinpirole are 1.0 μg/site and 2.0 μg/site,and the optimal action time is 5-50 min.Therefore,on the basis of economy,in the subsequent electrophysiological experiment,the selected dose was 1.0 μg/ site.2.Electrophysiological changes of GPe nuclei1)Classification of neurons in the GPeBased on the analysis of the original signal,waveform and firing interval histogram of the neurons in the GPe,the neurons can be divided into two types: HFP and LFB.HFP neurons are characterized by high-frequency discharges with discharge pauses,and LFB is characterized by low-frequency discharges with bursts.2)The firing rate and firing pattern of HFP and LFB neurons in PD rats were changed after administration of quinpiroleAccording to the analysis of neuronal electrical signals in the awake,static and continuous motion state of the rats,the firing rates of HFP and LFB neurons in the PD group decreased compared with the normal control group,and the CV value increased,and the firing pattern became irregular in both conditions.After quinpirole drug administration in PD group,the firing rate of HFP neurons increased,but the firing pattern still showed irregular changes.The firing rate of LFB neurons increased,and the CV value increased under the static state,but the firing mode still changed irregularly.There was no significant difference in CV value under the motion state.3.Electrophysiological changes of GPi1)Classification of GPi neuronsBased on the analysis of the original signal,waveform and firing interval histogram of the neurons in the GPi nucleus,it is found that there is only one type of neurons in GPi nucleus,and the firing characteristic of the neurons is the high frequency discharge with uniform discharge distribution and discharge pause.2)The firing rate and firing pattern of HFP and LFB neurons in PD rats were changed after administration of quinpiroleBy analyzing the electrical signals of neurons when the rats were awake,still and continuously moving,it was found that the firing rate of neurons in the GPi nucleus of the rats in PD group was increased,and the CV value was larger,and the firing pattern was more irregular,compared with the normal control group under two conditions.After drug intervention in PD group,the firing rate of neurons in the GPi nucleus was decreased in both awake,static and continuous motion state.After the treatment of quinpirole,CV increased slightly in the state of wakefulness and rest,but the discharge pattern was still irregular,and CV value did not change significantly in the state of continuous motion.4.Correlation analysis of GPe-GPi before and after administration of quinpiroleCompared with the control group,the pathological changes of the two nuclei of GPe and GPi in the frequency band of 0.5-12 Hz and 12-35 Hz were observed in the awake,stationary and continuous motion state of PD.The correlation was enhanced,the length of the mean phase angle vector value increased,and the phase angle distribution became discrete.After the intervention of quinpirole,the correlation between the two nuclei at 0.5-12 Hz and 12-35 Hz in the awake and resting state of the rats in the PD group was reduced,pathologies were alleviated,the length of the mean phase angle vector value became shorter,and the phase angle distribution became discrete.In the state of continuous motion,the correlation between the two nuclei also decreased between 0.5-12 Hz and 12-35 Hz.According to the analysis of phase locking results,after the intervention of quinpirole,the phase angle distribution of PD group rats became discrete and the length of the mean phase angle vector value increased.Conclusion: According to the behavioral experiment,the optimal action dose of quionpirole is 1.0 μg/site and the optimal action time is 5-50 min.From a behavioral perspective,quinpirole,a dopamine D2 agonist,improved motor impairment in PD rats within the effective dose range and played an effective role in improving behavior.Once the threshold dose was exceeded,a series of inhibitory effects were produced.From the electrophysiological point of view,after injecting quinpirole into the dorsolateral striatum of rats,the firing rate of HFP and LFB neurons in PD group and control group was increased,while the firing rate of GPi neurons was decreased.In addition,the correlation between GPe and GPi was significantly different before and after administration administration of quinpirole in the frequency band of 0.5-12 Hz and 12-35Hz... |
PDF Full Text Request