Subsensitivity of human β-adrenergic adenylate cyclase after salbutamol treatment of depression

Although numerous studies have suggested that depression may be associated with a reduction in synaptic noradrenaline in the brain, direct β-adrenergic receptor agonists have only recently been tested in the treatment of depression. Moreover, newer theories of antidepressant action suggest that a reduction in β-adrenergic receptor sensitivity is a better correlate of antidepressant treatment than noradrenaline turnover changes. Eleven depressed patients were treated with salbutamol, a β-2-adrenergic agonist, and β-2-adrenergic receptor sensitivity was evaluated before, during, and after treatment. β-Adrenergic receptor sensitivity was evaluated by measuring the plasma cyclic AMP increase after an IV dose of salbutamol. The β-adrenergic agonist exhibited antidepressant efficacy and induced subsensitivity of the β-adrenergic adenylate cyclase with a time course paralleling the antidepressant effects. The results support the concept that receptor sensitivity changes occur during antidepressant therapy.