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 induced by unilateral injection of 6-hydroxy-dopamine (6-OHDA) produced an extensive decline in [3H]mazindol binding in the ipsilateral caudate-putamen (CPu) and a small (7%) decline in [3H]glutamate binding to N-methyl-D-aspartate (NMDA) receptors in CPu. Sinemet treatment of 6-OHDA-injected rats further reduced the binding of [3H]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 [3H]mazindol binding in both hemispheres of rats receiving unilateral 6-OHDA injections. L-Dopa/ carbidopa treatment did not affect [3H]glutamate or [3H]mazindol binding in neurologically intact rats.
O'Dell
S J
SJ
Department of Psychobiology, University of California, Irvine 92717, USA.
Marshall
J F
JF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine