CHRONIC L-DOPA ALTERS STRIATAL NMDA RECEPTORS IN RATS WITH DOPAMINERGIC INJURY

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 indu ced by unilateral injection of 6-hydroxydopamine (6-OHDA) produced an extensive decline in [H-3]mazindol binding in the ipsilateral caudate- putamen (CPu) and a small (7%) decline in [H-3]glutamate binding to N- methyl-D-aspartate (NMDA) receptors in CPu. Sinemet treatment of 6-OHD A-injected rats further reduced the binding of [H-3]glutamate to NMDA receptors. The greatest reductions (-34%) occurred in the denervated C Pu, but moderate declines (-18% to -22%) were also observed in the CPu , nucleus accumbens and cingulate cortex of the intact hemisphere. Une xpectedly, chronic Sinemet treatment also caused a decrease in [H-3]ma zindol binding in both hemispheres of rats receiving unilateral 6-OHDA injections. L-Dopa/carbidopa treatment did not affect [H-3]glutamate or [H-3]mazindol binding in neurologically intact rats.