Effects of risperidone, clozapine and haloperidol on extracellular recordings of substantia nigra reticulata neurons of the rat brain

Risperidone has proven to be effective as an antipsychotic drug and has fewer extrapyramidal side-effects than classic neuroleptics. In addition to its dopamine D-2 receptor antagonistic properties, this antipsychotic agent is a potent 5-HT2 receptor antagonist. The atypical antipsychotic, clozapine, also possesses both dopamine D-2 and 5-HT2 receptor affinity next to affinities for other receptors. To gain an insight in the consequences for basal ganglia activity of treatment with these atypical neuroleptics vs. typical neuroleptics, the effects of cumulative doses of risperidone, clozapine and haloperidol on the firing rate of substantia nigra reticulata neurons were studied. Extracellular recordings were performed in chloralhydrate-anaesthetized male Wistar rats. Both risperidone (50-3200 mu g/kg i.v.) and clozapine (100-6400 mu g/kg i.v.) dose dependently decreased substantia nigra reticulata activity maximally to 70% of the basal activity. With both treatments, a dose of 800 mu g/kg was significantly effective. In contrast, haloperidol (12.5-800 mu g/kg i.v.) gradually induced a slight increase in substantia nigra reticulata activity, which was identical to the substantia nigra reticulata activity after saline treatment. Therefore, these results indicate that typical and atypical neuroleptics affect differentially the output of the basal ganglia in the substantia nigra reticulata. To evaluate the involvement of 5-HT2 receptors in the effect of risperidone, the 5-HT2 receptor agonist, quipazine (0.5 mg/kg i.p.), was administered 15 min preceding risperidone treatment. A 4-fold higher dose of risperidone was needed to significantly affect the substantia nigra reticulata firing rate. Thus, the 5-HT2 component of the effect of risperidone is, at least partly, responsible for the difference in effect on substantia nigra reticulata neurons in comparison to haloperidol. (C) 1997 Elsevier Science B.V.