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The effect of chronic and acute treatment with several antidepressant drugs and electroconvulsive shock (ECS) on the responsiveness of norepinephrine (NE) receptor coupled adenylate cyclase and beta‐adrenergic receptor binding sites in rat brain has been studied by several groups of investigators. It has been consistently reported that chronic administration (2 to 4 weeks of treatment) of antidepressant drugs or ECS causes a decreased accumulation of NE stimulated cyclic AMP accumulation in rat brain. It has also been reported that chronic treatment with antidepressant drugs or ECS causes decreased binding of (3H)dihydroalprenolol (DHA) or (125I)hydroxybenzylpindolol (I‐HYP) (ligands used for studies of beta‐adrenergic receptors) in rat brain. However, such effects are not observed after acute or single administration of these drugs or ECS. Since there appears to be a close correlation between the time course of the effects of these drugs on NE receptor coupled adenylate cyclase and beta‐adrenergic receptor binding, and since most of the antidepressant drugs tested thus far produce such effects, it has been suggested that down regulation or decreased responsiveness of beta‐adrenergic receptors may be related to the therapeutic effects manifested by antidepressant drugs. These observations offer the possibility that determination of beta‐adrenergic receptor responsiveness after chronic treatment with drugs may prove useful in the preclinical screening of potential antidepressant drugs. In this paper, studies related to down regulation of beta‐adrenergic receptors, including our own, are reviewed.
Drug Development Research – Wiley
Published: Jan 1, 1983
Keywords: beta‐adrenergic receptors; NE receptors; adenylate cyclase; cyclic AMP; antidepressant treatment; antidepressant drugs; ECS
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