Regulation of serotonin2 (5-HT2) receptors labeled with [3H]spiroperidol by chronic treatment with the antidepressant amitriptyline.
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.
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001665:Binding Sites; D002090:Butyrophenones / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium
D000928:Antidepressive Agents; D002090:Butyrophenones; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D014316:Tritium; D000639:Amitriptyline; D012701:Serotonin; D013134:Spiperone; D004082:Dihydroalprenolol