Korean J Psychopharmacol.  1997 Oct;8(2):218-223.

The Effect of Neuroactive Steroids on the GAVA-Benzodiazepine Receptor Complex

• Lee JB
• Park HB
• Lee JH
• Park KG
• Kim CS
• Suh HS
• Ha JH

Abstract

Pregnolone[5beta-pregnan-3alpha-ol-one(5beta3alpha)] and allopregnanolone [(5alpha-pregnan-3alpha-ol-20-one(5alpha3alpha))] are neuroactive steroids that are reduced metabolites of progesterone. It was reported that Neuroactive steroids may have anxiolytic and anticonvulsant action similar to benzodiazepines and barbiturates. Therefore, the present study was designed to assess the interaction of steroids with GABAA-benzodiazepine receptor complex. The effect of steroids on the ligands binding to GABAA receptor complex was investigated using rat cortices. 5beta3alpha and 5alpha3alpha enhanced the binding of [3H] flunitrazepam to GABAA receptor, but testosterone, progesterone and dexamethasone did not. GABA also showed the enhancement of [3H] flunitrazepam binding, but did not show the additive effect. Unlike to GABA, 5beta3alpha and 5alpha3alpha did not affect on the [3H] muscimol binding to rat cortices. From these findings, it can be concluded that Neuroactive steroids are potent positive modulators of the GABA A receptor, and do not act at GABA binding site.

Keyword

Neuroactive steroids; GABA(A)-benzodiazepine receptor complex

MeSH Terms

Animals
Barbiturates
Benzodiazepines
Binding Sites
Dexamethasone
Flunitrazepam
gamma-Aminobutyric Acid
Ligands
Muscimol
Pregnanolone
Progesterone
Rats
Receptors, GABA-A
Steroids*
Testosterone
Barbiturates
Benzodiazepines
Dexamethasone
Flunitrazepam
Ligands
Muscimol
Pregnanolone
Progesterone
Receptors, GABA-A
Steroids
Testosterone
gamma-Aminobutyric Acid