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