6R-TETRAHYDROBIOPTERIN PERFUSION ENHANCES DOPAMINE, SEROTONIN, AND GLUTAMATE OUTPUTS IN DIALYSATE FROM RAT STRIATUM AND FRONTAL-CORTEX

The effect of 6R-tetrahydrobiopterin (R-THBP) on neurotransmitter release was investigated using in vivo brain microdialysis in urethane-anesthetized rats. Perfusion of 1.0 mM R-THBP enhanced the level of dopamine output in dialysates collected from the striatum and frontal cortex. R-THBP perfusion also increased serotonin (striatum) and glutamate outputs (striatum and frontal cortex). Dopaminergic terminals in the striatum were destroyed unilaterally by continuous infusion of 6-hydroxydopamine (6-OHDA) using an osmotic minipump system. The effect of R-THBP administration on glutamate level was found to be almost completely suppressed in the 6-OHDA-lesioned side of striatum, while in the intact side of striatum the glutamate level in the dialysates responded normally to R-THBP perfusion. These results suggest that R-THBP may play a role in the mechanisms of release of dopamine, serotonin, and glutamate. The functioning of the catecholaminergic system probably mediates the increase in glutamate output due to R-THBP perfusion.