L-dopa induced increases in brain uric acid in an animal model of Parkinson's disease: a relationship to behavioral activation.
Rats with severe unilateral dopamine denervation (> or = 95% dopamine deficit), produced by intracerebral injection of 6-hydroxydopamine (6-OHDA) into the ventral tegmentum nigrostriatal dopamine neurons, were administered 25 mg/kg L-dopa (3,4-dihydroxyphenylalanine) methyl ester/2 mg/kg carbidopa. The neurochemical effects of the L-dopa treatment on uric acid in the cortex and striatum of the intact and 6-OHDA hemisphere were measured. In comparison to saline animals, uric acid concentrations in brain were increased in the L-dopa treated animals. There were no interhemispheric differences in the uric acid concentrations either in the L-dopa or in the saline treated animals. Interhemispheric differences were, however, observed in terms of the correlations obtained between L-dopa and uric acid concentrations in the intact vs. the 6-OHDA hemisphere. Statistically significant correlation coefficients were found in the striatal and cortex samples obtained from the 6-OHDA hemisphere. Furthermore, high correlation coefficients were observed between contralateral rotation frequencies and uric acid concentrations in the cortex and striatum of the 6-OHDA hemisphere. In contrast, only low and statistically non significant correlations were observed in the tissue samples obtained from the intact hemisphere. These observations suggest that L-dopa activation of the dopamine supersensitive receptors of the DA denervated hemisphere and the associated metabolism of purines with high energy phosphate bonds (e.g. ATP and GTP) increases uric acid as an end-product of purine metabolism. These findings are consistent with other findings indicating that uric acid in the brain can provide an index of metabolic activation in brain tissue.
Pinheiro-Carrera
M
M
University of Sao Paulo, Ribeirao Preto, Brazil.
Tomaz
C
C
Huston
J P
JP
Dai
H
H
Carey
R J
RJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013563:Sympathectomy, Chemical; D014527:Uric Acid / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D014527:Uric Acid; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine