Effect of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin on the extracellular levels of dopamine and serotonin in the rat striatum: a microdialysis study with tyrosine or tryptophan infusion.

The present study demonstrates the effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) on turnover of dopamine and serotonin (5-HT) in rat striatum during continuous infusion of the amino acids tyrosine and tryptophan. By monitoring with microdialysis, it was found that the increase in dopamine and homovanillic acid (HVA) concentrations in rat striatal extracellular fluid (ECF) induced by 6R-BH4 was further enhanced by the continuous infusion of tyrosine at a relatively low dose (1 mumol/min/kg) as compared with the concentration which saturates tyrosine hydroxylation. This dose of tyrosine alone did not induce the elevation of dopamine and HVA concentrations in ECF. In contrast, though the concentration of 5-HT and 5-HIAA in striatal ECF was gradually increased by tryptophan infusion, 6R-BH4 had no further effect. Although the higher output of dopamine into ECF was induced by the dialytic perfusion of 6R-BH4 via the microdialysis probe into striatum, tyrosine infusion had no further effect on dopamine concentration in the dialysates. The in vivo measurement of DOPA accumulation during NSD 1015 perfusion suggests that the enhancement of dopamine concentration in ECF induced by tyrosine infusion and 6R-BH4 might be attributable to an increase in tyrosine hydroxylase activity in striatum. Tryptophan hydroxylase was also activated by tryptophan infusion and/or 6R-BH4, however, it did not induce an increase in 5-HT concentration in striatal ECF.