1. ¹Department of Psychiatry, Ludwig-Maximilian-University, Munich, Germany
2. ²Tor Vergata University, IRCCS Santa Lucia, Rome, Italy

Correspondence: Dr R Rupprecht, Department of Psychiatry, Ludwig-Maximilian-University, Nussbaumstr.7, 80336 Munich, Germany. Tel: +49 89 5160 2770; Fax: +49 89 5160 5524; E-mail: rainer.rupprecht@med.uni-muenchen.de

Received 9 February 2004; Revised 22 June 2004; Accepted 16 August 2004; Published online 29 September 2004.

Abstract

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