Brain dopamine depleted by d-tetrahydropalmatine

l-Tetrahydropalmatine(l-THP) is a DA receptor antagonist, which could antagonize both contralateral rotation induced by amphetamine (Amp) and ipsilateral rotation challenged by apomorphine (Apo) in rats unilaterally lesioned by 6-OHDA. However, d-THP did not antagonize contralateral and ipsilateral rotations, and it did not manifest the Amp- or Apo-like rotation either, but it (50 or 100 mg/kg) potentiated the Amp-induced rotation ( +40% or 90%). This suggests that d-THP may deplete DA into cytoplasma, in which DA is released by Amp, and enhances the Amp action. Amp increased the spontaneous activity of mice, on the contrary, d-THP depressed this activity. When the mice were pretreated with d-THP 25, 50, 100 mg/kg, the excitation of Amp was potentiated markedly in dose-dependent way. This result was very similar to the potentiation of d-THP on the rotation induced by Amp. After injection of d-THP 50 mg/kg, the striatal DA level was decreased by 56% and HVA level increased by 133% concomitantly, whereas l-THP had no effect on the DA level under the same conditions. Therefore, the DA depletion was only observed in d-THP, and this effect was reversed by selegiline (20 mg/kg), a MAOI-B. The above findings further support the conclusion that d-THP is a DA depletor, and l-THP is a brain DA antagonist, which has been reported in our Laboratory.