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SJ Peroutka and SH Snyder
Recently, we reported that chronic administration of several antidepressants of different classes produced larger reductions in numbers of serotonin2 (5-HT2) receptors in rat brain labeled by [3H[spiroperidol than in beta adrenergic receptors. In the present study, we examine detailed properties of 5-HT2 receptor regulation by chronic treatment with amitriptyline. Chronic but not acute treatment with the tricyclic antidepressant amitriptyline reduces binding to 5- HT2 receptors by [3H]spiroperidol and beta adrenergic receptor binding of [3H]dihydroalprenolol in brain membranes. The decrease is time- dependent, gradually reversible and represents a change in the number of binding sites with no alteration in drug affinities for 5-HT2 receptors. The effect can be observed at daily doses of 2.5 mg/kg, similar to clinically effective doses in humans. At all doses and time intervals, the decrease in 5-HT2 receptors is more marked than the concurrent change in total beta adrenergic receptor binding. The properties of 5-HT2 receptor reduction after chronic antidepressant treatment indicate that this alteration could be associated with therapeutic response.
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