Effects Of Melatonin Receptors Agonist And Antagonist In 6-OHDA Induced Parkinson Rats

ObjectiveTo investigate the effects of melatonin receptor agonist and antagonist on the behavior,serum melatonin and dopaminergic neurons in substantia nigra of PD rats induced by 6-OHDA.MethodsA 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 4 groups: Control,Control + AG/LU,PD,PD + AG/LU.The rotational behavior was induced by APO after 2,4,and 6 weeks post lesion.The rats were injected(i.p.)melatonin receptor agonist or antagonist lasts for 2 and 4 weeks.The serum melatonin(MLT)levels were determined by enzyme-linked immunosorbent assay(ELISA).The changes of DA neurons in substantia nigra(SN)were assayed by imunohistochemical staining.Results1?APO-induced rotational behavior: After 2,4 and 6 weeks post lesion,the APO-induced rotations in PD and PD+AG/LU groups were higher than that in the corresponding control.The rotations in PD group were 2W<4W<6W(p<0.05).The rotations in PD/LU group were 2W<6W<4W(p<0.05).Two weeks after intraperitoneal injection melatonin receptor agonist(Agomelatine,AG)or antagonist(Luzindole,LU),the rotations in PD and PD/AG groups were lower than that in the PD/LU group(p<0.001).Four weeks after injection AG or LU,the rotations in the PD/AG group were lower than that in the PD and PD/LU groups(p<0.05).2?The concentration of serum MLT: After 2 weeks of AG or LU administration,the concentration of serum MLT in each group was all higher than that after 4 weeks administration.The concentration of MLT in Cont/LU group was significant lower than that in the Cont group(p<0.01);the Cont/AG and PD/AG groups were significant higher than that in the Cont/LU and PD/LU groups(p<0.05).The concentration of MLT in the PD groups were higher than that in the PD/AG groups(p<0.05)and PD/LU groups(p<0.001).After 4 weeks of AG or LU administration,the concentration of MLT in PD/LU groups were higher than Cont/LU groups(p<0.001)3?Immunohistochemical staining of Tyrosine hydroxylase(TH): After 2 and 4 weeks of AG or LU administration,the numbers of TH positive neurons on lesion side in PD and PD+AG/LU groups were significantly decreased comparing with the unlesion side(p<0.001);the numbers of TH positive neurons on lesion side in PD group were decreased comparing with PD/LU groups(p<0.05).The numbers of TH positive neurons were no statistical differences between the unlesion and lesion sides in each control groups.After 2 weeks of administration,the numbers of TH positive neurons on unlesion side in PD/AG groups were significantly decreased comparing with PD groups(p<0.05);the numbers of TH positive neurons on unlesion side in both the PD/AG and PD groups were significantly decreased comparing with the PD/LU groups(p<0.01).After 4 weeks of administration,the numbers of TH positive neurons on unlesion side in PD groups were significantly decreased comparing with PD/LU groups(p<0.05).Conclusion:MR agonist AG can improve the rotation behavior induced by APO in PD rats.Long-term administration of MR antagonist LU can protect the DA neurons in substantia nigra(SN).The concentration of serum MLT may be associated with PD movement symptoms,but may have no protective effects on DA neurons.