ATYPICAL NEUROLEPTIC PROPERTIES OF L-STEPHOLIDINE

Intravenous administration of l-stepholidine (SPD), a dopamine (DA) re ceptor antagonist, increased the firing rate of DA neurons located in the ventral tegmental area (VTA) and substantia nigra pars compacta (S NC) in both anaesthetized and paralyzed rats. However, with the increa se of dose, SPD selectively inhibited the firing activity of DA neuron s in the VTA but not in the SNC. The inhibition was reversed by the DA agonist apomorphine (APO), suggesting that it may be via the mechanis m of depolarization inactivation (DI). In rats, chronic administration of SPD for 21 d dose-dependently decreased the number of spontaneousl y active DA neurons in the VTA, of which effect was reversed by APO (i .v.). In contrast, the same treatment failed to affect the population of DA neurons in the SNC. Similarly, the acute treatment of SPD also d ecreased the number of spontaneously firing DA neurons in the VTA, but not in the SNC. SPD per se only induced very weak catalepsy. Its cata lepsy which was not in proportion to dosage was only observed in the d ose range of 10-40 mg/kg and lasted 15 min. SPD effectively antagonize d the APO (2 mg/kg, i.p.)-induced stereotypy. The above-mentioned resu lts suggest that SPD selectively inactivates the DA neurons in the VTA not in the SNC. SPD may associate with a low incidence of extrapyrami dal side-effects and may be ranked as a promising compound for searchi ng for a new kind of atypical neuroleptics.