L-DOPA INDUCED INCREASES IN BRAIN URIC-ACID IN AN ANIMAL-MODEL OF PARKINSONS-DISEASE - A RELATIONSHIP TO BEHAVIORAL ACTIVATION

Rats with severe unilateral dopamine denervation (greater than or equa l to 95% dopamine deficit), produced by intracerebral injection of 6-h ydroxydopamine (6-OHDA) into the ventral tegmentum nigrostriatal dopam ine neurons, were administered 25 mg/kg L-DOPA (3,4-dihydroxyphenylala nine) methyl ester/2 mg/kg carbidopa. The neurochemical effects of the L-DOPA treatment on uric acid in the cortex and striatum of the intac t and 6-OHDA hemisphere were measured. In comparison to saline animals , uric acid concentrations in brain were increased in the L-DOPA treat ed animals. There were no interhemispheric differences in the uric aci d 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 correl ation coefficients were found in the striatal and cortex samples obtai ned from the 6-OHDA hemisphere. Furthermore, high correlation coeffici ents were observed between contralateral rotation frequencies and uric acid concentrations in the cortex and striatum of the 6-OHDA hemisphe re. In contrast, only low and statistically non significant correlatio ns were observed in the tissue samples obtained from the intact hemisp here. These observations suggest that L-DOPA activation of the dopamin e supersensitive receptors of the DA denervated hemisphere and the ass ociated metabolism of purines with high energy phosphate bonds (e.g. A TP and GTP) increases uric acid as an end-product of purine metabolism . These findings are consistent with other findings indicating that ur ic acid in the brain can provide an index of metabolic activation in b rain tissue.