Reduced adrenergic receptors either postsynaptically in vivo or on the cell surface of cultured cells is one result of chronic treatment with antidepressants. Bürgi et al. determined that chronic treatment of cultured rat C6 glioblastoma cells with desipramine, a tricyclic antidepressant, inhibits the reappearance of green fluorescent protein (GFP)-tagged β1-adrenergic receptors (GFP-β1AR). Several preliminary studies were performed to show that the GFP tag did not interfere with ligand binding, with G protein coupling, or with receptor internalization or recycling in cells not exposed to desipramine. The GFP-β1AR did not accumulate in lysosomes after desipramine exposure; instead, the protein accumulated in a recycling compartment that colocalized with internalized transferrin receptors. Transferrin receptor recycling to the plasma membrane was not impaired by desipramine treatment. Thus, tricyclic antidepressants may decrease β1AR surface expression by altering receptor trafficking, instead of by prolonging agonist stimulation.