L-DOPA metabolism in cortical and striatal tissues in an animal model of parkinsonism.
Rats with unilateral 6-hydroxydopamine lesions of the midbrain tegmentum were treated with 25 mg/kg L-DOPA methyl ester/2 mg/kg carbidopa. The effects of the L-DOPA treatment upon serum, neocortical, and striatal L-DOPA and 3-O-methyl dopa (3-OMD) concentrations were measured. The highest L-DOPA and 3-OMD concentrations were obtained in the serum and in a ratio of approximately 2:1. In the brain, there was a uniform distribution of 3-OMD but L-DOPA concentrations were highly nonhomogeneous. Regression line equations for the statistically significant correlation coefficients between L-DOPA and tissue dopamine concentrations suggested that L-DOPA generated 50-60 times as much dopamine in the intact striatum as in cortex. The regional variation of L-DOPA concentration appears related to the capability of the brain tissue to generate and store dopamine from L-DOPA. In addition, the findings suggest that the behavioral ineffectiveness of L-DOPA in intact animals is related to its capacity to transform L-DOPA to tissue bound dopamine.
Carey
R J
RJ
Research and Development Service, VA Medical Center, Syracuse, NY 13210, USA.
Dai
H
H
Huston
J P
JP
Pinheiro-Carrera
M
M
Schwarting
R K
RK
Tomaz
C
C
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D007980:Levodopa / Q000097:blood / Q000378:metabolism*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D014443:Tyrosine; D007980:Levodopa; D016627:Oxidopamine; C008404:3-methoxytyrosine; D004298:Dopamine