Effects Of Dopamine D₂ Receptor Agonists And Antagonists On Serum Melatonin In Rats With Parkinson’s Disease Induced By 6-hydroxydopamine

Purpose:Parkinson’s Diseases（PD）is one of the common neurodegenerative diseases.The pathogenesis is still unclear and may be related to oxidative stress and inflammation.Previous studies in our laboratory have found that melatonin levels in PD rats increase with progression.Because the circadian rhythm of melatonin synthesis and dopamine are interdependent（mainly through the dopamine D₂ receptor）,therefore the purpose of this study was to investigate the effects of dopamine D₂ receptor agonist（Quinpirole,Quin）or antagonist（Raclopride,Ra）on 6-OHDA-induced PD rat model of dopamine and melatonin and its possible mechanism.Method:A hemi-parkinsonium PD model was established by a unilateral injection of 6-hydroxydopamine（6-OHDA）into the right medial forebrain bundle（MFB）.Animals were randomly divided into 6 groups.After successful model establishment,ALZET micropump was installed,and microperfusion normal saline（NS）/Raclopride/Quinpirole for 1W and stop microperfusion for 1W.After that,the rotation behavior was detected,and the serum melatonin concentration was detected by ELISA.The changes of dopaminergic neurons in the substantia nigra were detected by immunohistochemistry.The protein relative expression of dopamine transporter（DAT）in the striatum was detected by Western blot.Results:1.After giving the drug 1W and stop the drug 1W（4W after surgery）,the number of circles of rotation in rats in the PD/Quin group decreased significantly compared with that in the PD group（p<0.05）.The number of rotation in rats in the PD/Ra group increased significantly compared to those in the PD group（p<0.05）.2.After giving the drug 1W and stop the drug 1W（4W after surgery）,the serum melatonin concentration in the PD/Quin group was significantly lower than that in the PD group（p<0.05）,and the melatonin concentration in the PD/Ra group was significantly greater than that in the PD group（p<0.05）;the melatonin concentration in the Cont/Ra group was significantly greater than that in the Cont group（p<0.05）3.The immunohistochemical results showed that after the drug was given 1W and stop the drug 1W（4W after surgery）,the number of TH positive cells on the lesioned side of PD/Quin group was higher than that on the lesioned side of PD group（p<0.05）and the number of TH positive cells on the lesioned side of the PD/Ra group was lower than that on the lesioned side of the PD group（p<0.05）.4.After the drug was given 1W and stop the drug 1W（4W after surgery）,there was no significant difference in the expression of DAT protein between the unlesioned side and the lesioned side of Cont,Cont/Quin and Cont/Ra groups.The expression of the unlesioned side protein in the PD and PD/Ra groups was higher than that on the lesioned side（p<0.05）.There was no statistically significant difference in the expression of the unlesioned side and the lesioned side of the PD/Quin group.Conclusion:1.Dopamine D₂ receptor agonists can improve 6-OHDA-induced rotational behavior in PD rats.2.Dopamine D₂ receptor agonists can protect the 6-OHDA injured dopaminergic neurons in the substantia nigra parenchyma of PD rats.3.Dopamine D₂ receptor agonists may protect the neuronal cells damaged by 6-OHDA by regulating the balance of dopamine and melatonin in the body by promoting the secretion of dopamine.4.The continuous administration of the micro pump can directly act on the target site,which is a safe and quick method of administration.5.6-OHDA may induce downregulation of striatum DAT in PD rats.