Lack of effect of raphe lesions on serotonin S2 receptor changes induced by amitriptyline and desmethylimipramine.

Spiperone binding was studied in rat cortical and striatal homogenates by direct binding assay after chronic (10 mg/kg/day i.p. for 21 days) treatment with the tricyclic antidepressants amitriptyline (AMT) and desmethylimipramine (DMI). Both AMT (a potent serotonin reuptake inhibitor) and DMI (a weak serotonin reuptake inhibitor) treatment were associated with decreased specific binding of 3H-spiperone and 3H-mianserin in the cortex (markers for serotonin S2 receptors) of 31-45% of normal rats, but not the binding of 3H-spiperone in the striatum (a marker for dopamine D2 receptors). The same chronic treatment of raphe-lesioned rats with AMT or DMI produced equivalent (38-40%) decreased specific binding of these ligands in the cortex but no change in striatum. These results suggest that synaptic serotonin concentration may not be the factor responsible for the decreased number of spiperone binding sites observed after chronic antidepressant treatment.