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To examine the effects of chronic L-dopa treatment on excitatory amino acid receptors, rats with unilateral nigrostriatal injury and intact controls were treated for 21 days with Sinemet (L-dopa + carbidopa) or vehicle followed by a 3-day washout period. Nigrostriatal damage induced by unilateral injection of 6-hydroxydopamine (6-OHDA) produced an extensive decline in [ 3 H]mazindol binding in the ipsilateral caudate-putamen (CPu) and a small (7%) decline in [ 3 H]glutamate binding to N-methyl-D-aspartate (NMDA) receptors in CPu. Sinemet treatment of 6-OHDA-injected rats further reduced the binding of [ 3 H]glutamate to NMDA receptors. The greatest reductions (-34%) occurred in the denervated CPu, but moderate declines (-18% to -22%) were also observed in the CPu, nucleus accumbens and cingulate cortex of the intact hemisphere. Unexpectedly, chronic Sinemet treatment also caused a decrease in [ 3 H]mazindol binding in both hemispheres of rats receiving unilateral 6-OHDA injections. L-Dopa/carbidopa treatment did not affect [ 3 H]glutamate or [ 3 H]mazindol binding in neurologically intact rats.