Panic induction with cholecystokinin-tetrapeptide (CCK-4) increases plasma concentrations of the neuroactive steroid 3α, 5α tetrahydrodeoxycorticosterone (3α, 5α-THDOC) in healthy volunteers

Abstract

3α-reduced neuroactive steroids such as 3α, 5α-tetrahydroprogesterone (3α, 5α-THP) and 3α, 5α-tetrahydrodeoxycorticosterone (3α, 5α-THDOC) are potent positive allosteric modulators of γ-aminobutyric acid type A (GABA A) 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 3α, 5α-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3α, 5α-THDOC concentrations during experimental panic induction. Therefore, we quantified 3α, 5α-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 3α, 5α-THDOC, ACTH and cortisol concentrations. This increase in 3α, 5α-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.