3H-imipramine binding sites in brain down-regulated by chronic nortriptyline and haloperidol but not mianserin...

Specific binding of 3H-imipramine to membrane preparations from the cerebral cortex and hippocampus was measured in rats given nortriptyline (10 mg/kg/day), mianserin (10 mg/kg/day), haloperidol (1 mg/kg/day), or saline for 21 days and killed 48 hours after the last injection. Chronic treatment with nortriptyline resulted in a significant decrease in density (Bmax) of 3H-imipramine binding sites in the hippocampus but not in cerebral cortex without significant changes in binding affinity (Kd). Mianserin treatment failed to alter Bmax and Kd of specific 3H-imipramine binding in either of the two brain regions. Repeated administration of haloperidol also produced a lowering in the number of 3H-imipramine binding sites (Bmax) in the hippocampus. The results indicate that the ability of tricyclic antidepressants to down-regulate 3H-imipramine recognition sites in the brain is not shared by nontricylic antidepressants such as mianserin. The observation that down-regulation of binding can also be produced by a typical antipsychotic drug, haloperidol, suggests that this phenomenon may not be related to the mode of therapeutic effect of antidepressants.