Tricyclic antidepressants activate the pituitary-adrenal axis in the rat. Tolerance to repeated drug administration.
The effects of acute chronic administration of tricyclic antidepressants on the pituitary-adrenal axis were studied in adult male rats. Acute administration of desipramine, imipramine and chlorimipramine activated the pituitary-adrenal axis. The effect of imipramine was found to be of short duration with a significant increase at 30 and 60 min after the administration of the drug and a return to baseline levels at 180 min. The effect of imipramine was dose-dependent. Twenty hours after the last drug administration rats chronically injected with chlorimipramine showed normal basal and saline-induced levels of corticosterone. However the response of these rats to an acute dose of chlorimipramine was significantly lower than that of drug-naive rats, indicating tolerance to the drug. The mechanisms involved in the activation of the pituitary-adrenal axis caused by antidepressants and the tolerance to repeated drug administration are still unknown.
Armario
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A
Departamento de Biología Celular y Fisiología, Facultad de Ciencias, Universidad Autónoma de Barcelona, Spain.
García-Marquez
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C
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004361:Drug Tolerance; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000097:blood
D000929:Antidepressive Agents, Tricyclic; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone