Comparison of short-term administration of sertindole, clozapine and haloperidol on the inactivation of midbrain dopamine neurons in the rat.

The present study describes the effect of sertindole, clozapine and haloperidol on the number of spontaneously active dopamine neurons in ventral tegmental area and substantia nigra pars compacta after daily oral treatment for 1, 2 or 3 weeks. In general, daily administration of high dosages (sertindole: 2.8 mumol/kg/day, clozapine: 60 mumol/kg/day, haloperidol: 0.43 mumol/kg/day) induced no statistically significant decrease in the number of active dopamine neurons within the first 2 weeks of treatment. All three compounds induced a marked effect in ventral tegmental area after administration for 3 weeks, but only sertindole and haloperidol influenced the activity in substantia nigra pars compacta. This result is in accordance with clinical data where the antipsychotic effect is observed after 2-3 weeks of treatment.