Antipsychotics and single-cell activity in the rat superior colliculus

Schizophrenic patients have problems with saccadic eye movements that can be characterized as a loss of control over the saccadic system. Preliminary clinical results suggest that antipsychotics can either disrupt or improve saccadic performance. The brain mechanism through which antipsychotics might affect saccades is the subject of study. The superior colliculus (SC) is crucially involved in the generation of saccades. Previous experimental studies showed that the substantia nigra reticulata (SNr), a structure with profound inhibitory influence on the SC, is differentially affected by classical and atypical antipsychotics. In this study, we investigated the potential effects of atypical antipsychotics (clozapine, olanzapine, and risperidone) and a classical antipsychotic (haloperidol) on the firing rate of SC cells in the rat. In anesthetized rats, we performed extracellular recordings on spontaneous active neurons in the intermediate and deep layers of the SC. After subcutaneous injection of an antipsychotic drug, changes in firing rate were compared with responses upon saline injection. Olanzapine (1.0 mg/kg), risperidone (0.3 and 1.0 mg/kg), and haloperidol (0.5 mg/kg) did not significantly alter cell activity, but clozapine (10.0 mg/kg) induced a short-lasting but significant decrease. Except for clozapine, the effects of antipsychotics on the SC were nonsignificant and therefore independent of the effects in the SNr. Our results support the notion that clozapine is different from the other atypical antipsychotics.