Reduction of serotonin-2 receptors in rat cerebral cortex after subchronic administration of imipramine, chlorpromazine, and the combination thereof

Combined administration of antidepressant and neuroleptic drugs has been reported to have a synergistic effect in the treatment of psychotic depression. The effects of subchronic administration of imipramine, chlorpromazine, or the combination, on serotonin₂ (5-HT₂) receptors labeled by ³H-spiroperidol in rat cerebral cortex were studied to determine whether this synergism might be related to an effect on these receptors, which have been linked to the therapeutic action of antidepressants. Treatment with imipramine or chlorpromazine alone for 14 days decreased the density of 5-HT₂ receptor binding sites in rat cortex; the combination of the two drugs produced a greater reduction in 5-HT₂ binding sites than imipramine or chlorpromazine alone. Thus, the clinical synergism of this combination may be related, in part to the more extensive decrease in 5-HT₂ binding sites it produces. The ability of chlorpromazine alone to decrease 5-HT₂ binding sites might be relevant to reports that it has an independent antidepressant action.