Inhibitory effect of diazepam on the activity of the hypothalamic-pituitary-adrenal axis in female rats.
The acute intraperitoneal administration of anxiolytic diazepam (2 mg/kg) inhibits the activity of the hypothalamic-pituitary-adrenal (HPA) axis, i.e., it decreases the concentration of adrenocorticotropic hormone (ACTH) and corticosterone in female rats. This fall of ACTH and corticosterone levels was reversed by an antagonist of central benzodiazepine receptors-flumazenil. The antagonist of peripheral benzodiazepine receptors-PK 11195, failed to affect diazepam-induced decrement of plasma ACTH and corticosterone levels. The suppressed HPA function obtained after diazepam administration was also antagonized by bicuculline, an antagonist of GABA recognition sites, and by picrotoxin, a drug that blocks the GABA-A receptor associated chloride channel. These results suggest that central benzodiazepine receptors, the part of GABA-A macromolecular complex, are involved in diazepam-induced inhibition of the activity of the HPA axis.
Ruder Bosković Institute, Zagreb, Croatia.
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Pivac
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Pericić
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003864:Depression, Chemical; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects
D000324:Adrenocorticotropic Hormone; D001640:Bicuculline; D003345:Corticosterone; D003975:Diazepam; D005442:Flumazenil; D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; D010852:Picrotoxin; D011963:Receptors, GABA-A; C037850:PK 11195