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 v entral tegmental area and substantia nigra pars compacta was determine d. Standard electrophysiological measurements (i.e. single unit record ing technique) were used. Risperidone, olanzapine and amperozide showe d some selectivity (at one particular dose) for decreasing the number of active dopamine neurons in the ventral tegmental area. However, ris peridone induced a U-shaped dose-response curve. The highest dose of a mperozide inhibited the activity in substantia nigra pars compacta, sh owing a liability to induce extrapyramidal side-effects. Seroquel and ziprasidone inhibited the activity in both areas indicating a classica l antipsychotic profile (i.e. high liability to cause extrapyramidal s ide-effects).