Biphasic actions of L-DOPA on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices.

Effects of L-DOPA on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices evoked by electrical field stimulation at 5 Hz were investigated in the absence and presence of p-bromobenzyloxyamine (NSD-1055), a DOPA-decarboxylase inhibitor. In the absence of NSD-1055, L-DOPA produced a facilitation of impulse-evoked release of noradrenaline at 0.1 microM but not at 1 and 10 microM, and had no effect on the spontaneous release. On the other hand, L-DOPA 0.1 to 10 microM dose-dependently increased the spontaneous release of dopamine and the highest concentration only increased the evoked release and tissue content of dopamine. In the presence of NSD-1055 10 microM, the increase in the spontaneous release of dopamine was prevented and L-DOPA produced biphasic regulatory effects on the evoked release of noradrenaline and dopamine, a facilitation at 0.1 microM and an inhibition at 1 microM. The facilitation was antagonized by (-)-propranolol 0.1 microM, but not by the (+)-isomer, whereas the inhibition was antagonized by S-sulpiride 1 nM, but not by the R-isomer. In conclusion, L-DOPA appears to produce biphasic actions on the release of endogenous noradrenaline and dopamine from rat hypothalamic slices, not through its conversion to dopamine but through presynaptic regulatory mechanisms, an inhibition via dopamine receptors at a micromolar concentration and a facilitation via beta-adrenoceptors at the lower concentration.