Pharmacopsychiatry 2005; 38 - A056
DOI: 10.1055/s-2005-918678

Plasma concentrations of the neuroactive steroid 3α, 5α tetrahydrodeoxycorticosterone (3α, 5α-THDOC) after panic induction with cholecystokinin-tetrapeptide (CCK–4) in healthy volunteers

D Eser 1, F di Michele 2, PM Zwanzger 3, TC Baghai 3, C Schüle 3, A Pasini 4, E Romeo 5, R Rupprecht 3
  • 1Ludwig-Maximilians-Universität LMU München, Klinik und Poliklinik für Psychiatrie und Psychotherapie, München
  • 2Tor Vergata University IRCCS Santa Lucia, Rome, Italy
  • 3Klinik für Psychiatrie und Psychotherapie, Ludwig Maximilians Universität München
  • 4Tor Vergata University, IRCCS Santa Lucia, Rome, Italy
  • 5Tor Vergata University IRCCS Santa Lucia, Rome, Italy

In addition to the well-known genomic effects of steroid molecules certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3α-reduced steroids are potent positive allosteric modulators of the γ-aminobutyric acid type A (GABAA)-receptor. In line with their GABA enhancing potential, a pronounced anxiolytic activity has been shown for 3α-reduced neuroactive steroids in various animal studies.

Experimental panic induction with cholecystokinin-tetrapeptide (CCK–4) is accompanied by a decrease in 3α, 5α-THP concentrations in patients with panic disorder but not in healthy controls. While various studies show an increase in ACTH and cortisol secretion following challenge with CCK–4, no data are available on 3α, 5α-THDOC levels during experimentally induced panic in humans.

Therefore, we quantified 3α, 5α-THDOC concentrations in 10 healthy volunteers (9 men, 1 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 panicogenic response as assessed by the Acute Panic Inventory (API). 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-pituary adrenal axis activation following CCK–4 induced panic and might contribute to the termination of the anxiety/stress response during this challenge procedure.