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1.The effects of age and of chronic antidepressant treatment on [3H]tryptamine and [3H]dihydroalprenolol binding site density were measured in brain cortical membranes from male Sprague-Dawley rats.2.The density but not the affinity of [3H]tryptamine binding sites was increased in 18-month-old rats relative to 3-month-old rats. Neither the density nor the affinity of [3H]dihydroalprenolol binding sites was affected by age.3.Chronic administration (28 days s.c. via Alzet osmotic minipumps) of tricyclic antidepressant drugs (daily doses: imipramine·HCl, 30 mg kg-1; desipramine·HCl, 10 mg kg-1; clomipramine·HCl, 10 mg kg-1) resulted in decreases in [3H]dihydroalprenolol binding site density but no changes in [3H]tryptamine binding site density; no changes in affinity of either site were observed.4.Chronic administration (s.c. via Alzet osmotic minipumps) of monoamine oxidase inhibitor antidepressant drugs (daily doses: tranylcypromine·HCl, 0.5 and 1.0 mg kg-1; phenelzine sulfate, 5 and 10 mg kg-1, each for 28 days; clorgyline·HCl, 1.0 mg kg-1; (-)-deprenyl·HCl, 1.0 mg kg-1, each for 14 days) resulted in decreases in [3H]tryptamine binding site density, without any effects on the affinity of this site. In addition, each of these monoamine oxidase inhibitors except (-)-deprenyl resulted in a decrease in [3H]dihydroalprenolol binding site density. No affinity changes were observed.5.These data indicate that the [3H]tryptamine binding site exhibits physiological changes with aging and is differentially sensitive to the actions of tricyclic antidepressants and monoamine oxidase inhibitor antidepressants, respectively.