Comparison of effects of tetrahydropalmatine enantiomers on firing activity of dopamine neurons in substantia nigra pars compacta.

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.