Adenosine A2A antagonism reverses levodopa‐induced motor alterations in hemiparkinsonian rats

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Abstract
To evaluate the possible involvement of adenosine A2A receptor-mediated mechanisms in levodopa-induced motor fluctuations, we investigated the effects of CSC (8-(3-chlorostryryl) caffeine), a selective adenosine A2A 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 A2A receptor antagonist CSC reverses but does not prevent levodopa-induced motor alterations in parkinsonian rats. These results suggest a role for adenosine A2A receptor-mediated mechanisms in the pathophysiology of levodopa-induced motor response complications. These findings suggest that the antagonism of adenosine A2A receptors might confer clinical benefit to parkinsonian patients under levodopa therapy suffering from motor complication syndrome. Synapse 46:251–257, 2002.
Funding Information
  • Ministerio de Sanidad y Consumo of the Spanish Government (FIS 00/0151)
  • Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)