Extracellular single unit recording techniques were used to elucidate the effects of enantiomers of tetrahydropalmatine (THP) on the firing activity of dopamine (DA) neurons in substantia nigra pars compacta (SNC). (-)-THP rapidly reversed the apomorphine (Apo)-induced inhibition of the SNC DA cell firing activity (ED50 = 0.77, 0.52-1.14, mg.kg-1), while much larger doses of (+)-THP were required to reverse the Apo-induced inhibition (ED50 = 23, 15.2-34.7, mg.kg-1) and the maximal reversal caused by (+)-THP was 79 +/- 9% of the basal firing rate. In paralyzed rats, (-)-THP (0.5-16 mg.kg-1) significantly increased the spontaneous firing rate of SNC DA neurons dose-dependently, while (+)-THP did not until the dose reached 16 mg.kg-1. Pretreatment with (-)-THP 4 mg.kg-1 attenuated Apo-induced inhibition of SNC DA cell firing rate, while (+)-THP 32 mg.kg-1 revealed a similar potency to block the Apo-induced inhibition. In addition, (+)-THP did not potentiate the effect caused by d-amphetamine (Amp) as some behavioral experiments have shown, but large dose of (+)-THP (32 mg.kg-1) blocked the Amp-induced inhibition of SNC DA cell firing activity as (-)-THP (4 mg.kg-1) did. These results suggest that the interaction between D2 receptors and THP enantiomers has stereoselectivity and that (-)-THP is a D2 antagonist while (+)-THP seems to be not.