Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3alpha, 5alpha tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers.
3alpha-reduced neuroactive steroids such as 3alpha, 5alpha-tetrahydroprogesterone (3alpha, 5alpha-THP) and 3alpha, 5alpha-tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3alpha, 5alpha-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3alpha, 5alpha-THDOC concentrations during experimental panic induction. Therefore, we quantified 3alpha, 5alpha-THDOC concentrations in 10 healthy volunteers (nine men, one woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response as assessed by the Acute Panic Inventory. This was accompanied by an increase in 3alpha, 5alpha-THDOC, ACTH and cortisol concentrations. This increase in 3alpha, 5alpha-THDOC might be a consequence of hypothalamic-pituitary-adrenal (HPA) axis activation following CCK-4-induced panic, and might contribute to the termination of the anxiety/stress response following challenge with CCK-4 through enhancement of GABAA receptor function.
Eser
Daniela
D
Department of Psychiatry, Ludwig-Maximilian-University, Munich, Germany.
di Michele
Flavia
F
Zwanzger
Peter
P
Pasini
Augusto
A
Baghai
Thomas C
TC
Schüle
Cornelius
C
Rupprecht
Rainer
R
Romeo
Elena
E
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000097:blood*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010200:Panic / Q000187:drug effects* / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D013256:Steroids / Q000097:blood; D013758:Tetragastrin
D013256:Steroids; D013758:Tetragastrin; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone