This paper reviews briefly the very common finding in chronic antidepressant use, of subsensitivity of the β-adrenoreceptor-linked cyclic AMP system. This subsensitivity is observed with a number of different antidepressant treatments, including pharmacological, electrical and sleep deprivation. The subsensitivity requires intact noradrenergic and serotonergic systems, functionally linking the two neurotransmitters most often implicated in depression. Thyroid hormones and estrogens also cause subsensitivity, while the opposite effect is seen with Reserpine and Propranolol. A modified conditioning/sensitization model is proposed, implicating psychosocial stressors with a biological inability to down-regulate β-adrenoreceptors.
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