Effects Of Adenosine A_2A Receptor On The Dyskinesia Induced By L-DOPA In Parkinson's Disease Rat Model

Partâ… Establishment of the PD Rat Model of Levodopa Induced Dyskinesias and the Behavioral InvestigationObjective To establish the PD rat model of the levodopa induced dyskinesia (LID) with the application of L-DOPA and 6-OHDA and investigate their behavioral characteristics.Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to right medial forebrain bundle (MFB). After two weeks, apomorphine-induced rotation test was performed to examine the rat model of PD. Animals were intraperitoneally treated by NS and L-DOPA (25mg/kg+6.25mg/kg benserazide) respectively twice daily for 21 days. On the 2nd day, 9th day, 11th day, 18th day and the 21st day during the treatment, forepaw adjusting steps, AIM and rotational duration were respectively observed. The quality of AIM was estimated by using the rat AIM rating scale.Results Of the twenty successful rat PD models, ten were given NS treatment, while the other ten L-DOPA treatment. Contralateral forepaw performance was significantly improved after levodopa treatment, not NS treatment, but gradually reduced with more and more severe AIM following repeated levodopa therapy. The treatment of levodopa gradually induced abnormal involuntary movement (AIM) and the score of AIM gradually increased. Rotation duration was shortened significantly. On the 21st day, the AIM Score increased compared to the 2nd day. Rotation duration was shortened significantly.Conclusion Levodopa induced rat AIM model of PD was similar to that with the levodopa-induced dyskinesia (LID) in PD patients, which provided an ideal model for LID study.Partâ…¡The Effects of CSC on the Behavior and the Striatal A_2AR,mGluR₅ Protein Expression on Dyskinesia Induced by L-DOPA in Parkinson's Disease Rat ModelObjective To investigate behavioural and biological effects of adenosine A_2A receptor antagonist-CSC in a rat model of levodopa-induced motor complications.Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to the right medial forebrain bundle(MFB). Animals were intraperitoneally treated with NS, levodopa 25 mg/kg plus benserazide 6.25 mg/kg, CSC 2.5mg/kg and CSC 2.5mg/kg + levodopa 25 mg/kg plus benserazide 6.25 mg/kg respectively, twice a day for 21 days. Forepaw adjusting steps and AIM and rotational duration were respectively observed. The quality of AIM was estimated by using the rat AIM rating scale. After sacrificed, the expression of adenosine A_2A receptor and mGluR₅ was observed by Western blot.Results 1 Chronic administration of A_2A antagonists produced a relief of motor disability (as assessed in Forepaw adjusting steps ), which did not exhibit tolerance over at least 21 days of treatment. 2 Co-administration of L-DOPA and CSC result in a significant improvemen in motor disability and rotary performance compared with L-DOPA alone, at the same time attenuated the severity of limb, orolingual AIMs. 3 CSC was not accompanied by manifestations of abnormal, excessive movement (as evaluated in this study using ratings of axial, limb, orolingual and locomotive AIMs) when given alone. 4 The chronic levodopa treatment upregulated the striatal adenosine A_2AR and mGluR₅ expression , however, the CSC treatment attenuated the levodopa-induced these receptors upregulation. Conclusion 1 Adenosine A_2A receptor was involved in the development of Parkinson's disease and the motor complications induced by levodopa and adenosine A_2A receptor antagonist could be useful in the treatment of the motor deficit and motor complications in parkinsonian patients. 2 That the treatmen of adenosine A_2A receptor antagonist affect the striatal mGluR₅ expression was an indication of the mGluR₅ as the potential target of Parkinson's disease and dyskines induced by levodopa.