The effects of adenosine A2A receptor antagonist on the behavior and the striatal A2A receptor,metabotropic glutamate receptors protein expression in rats with levodopa-induced dyskinesia
10.3760/cma.j.issn.1006-7876.2011.02.012
- VernacularTitle:腺苷A2A受体拮抗剂对左旋多巴诱发异动症大鼠行为、纹状体A2A受体和代谢型谷氨酸受体5亚型蛋白表达的影响
- Author:
Yixian HUANG
;
Dan LI
;
Weifeng LUO
;
Chunfeng LIU
- Publication Type:Journal Article
- Keywords:
Dyskinesia,drug-induced;
Caffeine;
Receptor,adenosine A2A;
Receptor,metabotropic glutamate;
Levodopa;
Rats
- From:
Chinese Journal of Neurology
2011;44(2):122-127
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the behavioural changes and biological effects of selective adenosine A2A receptor antagonist (CSC) in a rat model of levodopa(L-DOPA) -induced dyskinesia (LID).Methods The hemi-parkinsonian rat model was produced by stereotaxically injecting 6-OHDA to the right medial forebrain bundle. Rats were randomly divided into 4 treatment groups with a random number generating program to receive intraperitoneal injections twice daily for 21 days (n = 10): saline, L-DOPA at 25 mg/kg with benserazide at 6. 25 mg/kg, CSC at 2. 5 mg/kg alone and CSC at 2.5 mg/kg with L-DOPA at 25 mg/kg plus benserazide at 6. 25 mg/kg. Forepaw adjusting steps, abnormal involuntary movements (AIM) and rotational response duration were observed on 2, 9, 11,18 and 21 d. After sacrifice, the expression of adenosine A2A R and mGluR5 was observed by Western blot. Results Co-administration of LDOPA with CSC significantly increased the forelimb adjusting steps of parkinsonian rats during 21 days of treatment when compared to L-DOPA alone. CSC treatment alone increased the forelimb adjusting steps significantly. Co-administration of L-DOPA with CSC ( ( 11 ± 5 ) score) significantly decreased the AIM scores of limb and orolingual muscles when compared to L-DOPA alone (( 17 ± 4) score; t = 2. 44, P ＜0. 05). The subchronic L-DOPA treatment upregulated the striatal expression of adenosine A2A R and mGluR5. However, co-administration of L-DOPA with CSC reversed the shortening of the rotational motor response duration induced by L-DOPA administration during the period of the treatment and attenuated the LDOPA-induced upregulation of adenosine A2A R and mGluR5 expressions. Conclusions CSC improves motor function in a hemi-parkinson rat model, potentiates the antiparkinsonian effects with L-DOPA and partly attenuates LID. Co-administration of L-DOPA with CSC reverses the L-DOPA-induced upregulated expression of A2A R and mGluR5, indicating the involvement of both A2A R and mGluR5 in the onset and progression of LID. Adenosine A2AR antagonists may be promising drugs for treatment of LID.
