Stress-induced increase in brain neuroactive steroids: antagonism by abecarnil

Pharmacol Biochem Behav. 1996 May;54(1):205-10. doi: 10.1016/0091-3057(95)02133-7.

Abstract

Acute foot shock stress elicits a selective and time-dependent increase of neuroactive steroid (pregnenolone, progesterone, allotetrahydrodeoxycorticosterone) concentrations in rat brain cortex, accompanied by a marked increase of plasma corticosterone. The brain cortical neuroactive steroid levels peaked between 10 and 30 min poststress and returned to control values by 2 h. Abecarnil (0.3 mg/kg), i.p.), a beta-carboline derivative with anxiolytic properties, completely antagonized the effect of foot shock on brain cortical neuroactive steroids. A single administration of the anxiogenic beta-carboline FG 7142 (15 mg/kg, i.p.), in contrast, mimicked the effect of foot shock. These data support the hypothesis for the existence of a functional relationship between brain neuroactive steroid concentrations and GABAA receptor function/emotional state of the animal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Brain Chemistry / drug effects
  • Brain Chemistry / physiology*
  • Carbolines / pharmacology*
  • Carbon Dioxide / toxicity
  • Electroshock
  • GABA-A Receptor Antagonists
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects
  • Steroids / metabolism*
  • Stress, Psychological / metabolism*
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Anti-Anxiety Agents
  • Carbolines
  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • Steroids
  • Carbon Dioxide
  • gamma-Aminobutyric Acid
  • abecarnil