Differential effects of repeated administration of novel antipsychotic drugs on the activity of midbrain dopamine neurons in the rat

Five potential antipsychotics (i.e. risperidone, olanzapine, seroquel, ziprasidone and amperozide) were given daily for 21 days to rats and the effect on the number of spontaneously active dopamine neurons in ventral tegmental area and substantia nigra pars compacta was determined. Standard electrophysiological measurements (i.e. single unit recording technique) were used. Risperidone, olanzapine and amperozide showed some selectivity (at one particular dose) for decreasing the number of active dopamine neurons in the ventral tegmental area. However, risperidone induced a U-shaped dose-response curve. The highest dose of amperozide inhibited the activity in substantia nigra pars compacta, showing a liability to induce extrapyramidal side-effects. Seroquel and ziprasidone inhibited the activity in both areas indicating a classical antipsychotic profile (i.e. high liability to cause extrapyramidal side-effects).