Adenosine A2A antagonism reverses levodopa-induced motor alterations in hemiparkinsonian rats
Adenosine A2A antagonism reverses levodopa-induced motor alterations in hemiparkinsonian rats
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DOI：
10.1002/syn.10112
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发表时间：
2002-12-15
期刊：
影响因子：
2.3
通讯作者：
Tolosa, E
中科院分区：
文献类型：
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作者：
Bové, J;Marin, C;Tolosa, E
为了评价腺苷A(2A)受体介导的机制在左旋多巴引起的运动波动中的可能作用，我们观察了选择性腺苷A(2A)受体拮抗剂CSC(8-(3-氯士林)咖啡因)对左旋多巴诱导的单侧6-OHDA损伤大鼠运动变化的影响。对CSC的急性和慢性给药进行了研究，以评估这些左旋多巴作用的逆转或预防的可能性。在第一组实验中，大鼠被给予左旋多巴(25毫克/公斤，每日两次，ip)。22天和第23天CSC(5 mg/kg，i.p.)就在左旋多巴之前给药。在第二组实验中，大鼠连续22天每天服用左旋多巴和CSC(5毫克/公斤/天)。22天后，慢性左旋多巴诱发的旋转行为持续时间缩短(P<；0.05)。第23天给予CSC可逆转左旋多巴引起的运动反应时程缩短(P<；0.01)。慢性CSC给药不能阻止左旋多巴引起的反应时程缩短。我们的结果表明，腺苷A(2A)受体拮抗剂CSC逆转但不能阻止左旋多巴诱导的帕金森病大鼠的运动改变。这些结果提示腺苷A(2A)受体介导的机制在左旋多巴诱导的运动反应并发症的病理生理学中起作用。这些结果提示，腺苷A(2A)受体的拮抗作用可能对接受左旋多巴治疗的运动并发症综合征帕金森病患者有临床意义。(C)2002年Wiley-Liss，Inc.
To evaluate the possible involvement of adenosine A(2A) receptor-mediated mechanisms in levodopa-induced motor fluctuations, we investigated the effects of CSC (8-(3-chlorostryryl) caffeine), a selective adenosine A(2A) receptor antagonist, on levodopa-induced motor alterations in rats with unilateral 6-OHDA lesion. Acute and chronic administration of CSC was studied to evaluate the possible reversion or prevention of these levodopa effects. In a first set of experiments, rats were treated with levodopa (25 mg/kg with benserazide, twice daily, i.p.) for 22 days and on day 23 CSC (5 mg/kg, i.p.) was administered immediately before levodopa. In a second set of experiments, rats were treated daily for 22 days with levodopa and CSC (5 mg/kg/day, i.p.). The duration of the rotational behavior induced by chronic levodopa decreased after 22 days (P < 0.05). Acute administration of CSC on day 23 reversed levodopa-induced shortening in motor response duration (P < 0.01). Chronic CSC administration did not prevent the shortening in response duration induced by levodopa. Our results demonstrate that the adenosine A(2A) receptor antagonist CSC reverses but does not prevent levodopa-induced motor alterations in parkinsonian rats. These results suggest a role for adenosine A(2A) receptor-mediated mechanisms in the pathophysiology of levodopa-induced motor response complications. These findings suggest that the antagonism of adenosine A(2A) receptors might confer clinical benefit to parkinsonian patients under levodopa therapy suffering from motor complication syndrome. (C) 2002 Wiley-Liss, Inc.