REGULATION OF SEROTONIN-2 (5-HT2) RECEPTORS LABELED WITH [H-3]SPIROPERIDOL BY CHRONIC TREATMENT WITH THE ANTI-DEPRESSANT AMITRIPTYLINE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 215  (3) , 582-587
Abstract
Recently, it was 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. Detailed properties of 5-HT2 receptor regulation by chronic treatment with amitriptyline were studied. 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 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.