Effect of l-tetrahydropalmatine on dopamine release and metabolism in the rat striatum

In vivo voltammetric measurements of striatal extracellular DOPAC concentrations and of striatal DA release in combination with post-mortem analysis of striatal catechols were performed in the rat to study the effects on the nigro-striatal neurons of a Chinese neuroleptic, l-tetrahydropalmatine (l-THP), which is known to block post-synaptic dopaminergic receptors. l-THP injected at doses that cause sedation in rats and mice (5-10 mg/kg) induced a marked increase in post-mortem DOPAC levels (+250%), while no significant effect was observed on postmortem DA levels. The extracellular DOPAC concentration was increased to 155 +/- 9% of the control value after l-THP administration (1 mg/kg, IP). Further, an injection of l-THP (1 mg/kg, IP) induced an increase in extracellular DA concentration (220% of the basal value), reversed the decrease in extracellular DA concentration induced by apomorphine (0.05 mg/kg, SC) and enhanced the effects of the electrical stimulation of the nigro-striatal pathway. These results confirm that l-THP acts on the nigro-striatal neurons as a dopaminergic antagonist that can block both post- and presynaptic receptors.