Effects of clozapine and haloperidol on 5-HT6 receptor mRNA levels in rat brain

The high affinity of 5-HT6 receptors for atypical antipsychotic drugs, and their localization in limbic and cortical regions of the brain, suggest that they might play a role in the pathophysiology of schizophrenia. To determine if this receptor is regulated by antipsychotics, rats were injected with clozapine (20 mg/kg/day), haloperidol (2 mg/kg/day), or vehicle daily for 2 weeks, and 5-HT6 receptor mRNA levels were measured by in situ hybridization. Clozapine but not haloperidol significantly decreased 5-HT6 expression in all subfields of the hippocampus. No drug effects were observed in cortical or forebrain structures. These results suggest that downregulation of this receptor in the hippocampus might be a characteristic of atypical antipsychotic drugs, although this hypothesis will require testing with other atypical antipsychotics.