Long-term effects of olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions

Rationale: Serotonin (5-HT) and its receptors have been implicated in various neuropsychiatric disorders. Altered serotonergic neurotransmission and interactions between 5-HT and dopamine (DA) systems may contribute to the pathophysiology of idiopathic psychotic or manic disorders. Interactions with 5-HT receptors may also contribute to special properties of modern antipsychotic drugs not yet evaluated for long-term effects on 5-HT receptors. Objective and methods: We surveyed effects of newer atypical antipsychotics on 5-HT receptor types 1A, 2A, and 2C in rat forebrain regions by quantitative receptor autoradiography with selective radioligands following 28 days of continuous infusion of drugs or control vehicle. Results: Infusion of olanzapine, risperidone, and quetiapine increased 1A, but decreased 2A receptor labeling in frontal cerebral cortex. Olanzapine decreased binding at 2C receptors in hippocampal CA(1) and CA(3) regions and perhaps entorhinal cortex; olanzapine, but neither risperidone nor quetiapine, also decreased 2C labeling in caudate-putamen. Conclusions: The findings suggest that altered 5-HT1A and 5-HT2A receptor levels in frontal cortex, and 5-HT2C receptors in other forebrain regions, may contribute to psychopharmacological properties of these novel atypical antipsychotic agents, perhaps including their antipsychotic or antimanic actions, and low risk of adverse extrapyramidal effects.