Effects of antiglucocorticoid treatment on 5-HT1A function in depressed patients and healthy subjects.
Clinical studies suggest that 5-HT1A receptor function may be blunted in depression, while 5-HT1A agonists may possess antidepressant activity. Preclinical findings implicate changes in 5-HT1A receptor sensitivity in the mechanism of antidepressant action. The hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in depression could be related to those observations, since 5-HT1A receptors are inhibited by glucocorticoids. To evaluate the interaction of the HPA and 5-HT1A systems, we pretreated 15 unipolar depressed patients and 12 healthy control subjects with the antiglucocorticoid ketoconazole (KTCZ) prior to administration of a test dose of the 5-HT1A agonist ipsapirone (IPS). Neuroendocrine (ACTH, cortisol, growth hormone), physiological (hypothermia), and behavioral responses to IPS were assessed. As expected, KTCZ inhibited cortisol biosynthesis, but non-HPA responses to IPS were not enhanced. This study failed to show that glucocorticoid modulation of 5-HT1A receptor function is altered in depression.
Price
L H
LH
Butler Hospital, Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI 02906, USA.
Cappiello
A
A
Malison
R T
RT
McDougle
C J
CJ
Pelton
G H
GH
Schöllnhammer
G
G
Heninger
G R
GR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D003866:Depressive Disorder / Q000378:metabolism*; D004311:Double-Blind Method; D005246:Feedback / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D013006:Growth Hormone / Q000097:blood; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000097:blood / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000097:blood / Q000494:pharmacology
D005938:Glucocorticoids; D006727:Hormone Antagonists; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C043077:ipsapirone; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D007654:Ketoconazole; D006854:Hydrocortisone