Chronic clozapine treatment down-regulates serotonin 5-HT-1c receptors in rat brain

1. The effects of chronic treatment with the atypical antipsychotic, clozapine, and classical antipsychotic, haloperidol, on serotonergic 5-HT-1c and dopamine D2 receptors in rat brain were studied with radioligand binding methods. 2. Two weeks' treatment with clozapine did not alter striatal D2 receptor characteristics measured with 3H-spiperone, but caused a 54% down-regulation of 3H-mesulergine binding to 5-HT-1c receptors in choroid plexus. 3. In contrast, two weeks' treatment with a classical neuroleptic, haloperidol increased significantly D2 receptor number in striatum, but had no effect on 5-HT-1c receptor binding. 4. In conclusion, alterations of 5-HT-1c receptor characteristics after chronic clozapine treatment may represent a mechanism that contributes to the unique clinical profile of this antipsychotic drug.