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 serotonin 2 (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.