J Korean Neuropsychiatr Assoc.  1999 May;38(3):656-663.

The Effect of Repeated Stress on the Modulation of Neuroactive Steroids at the GABAA-Benzodiazepine Receptor Complex in Rats

Affiliations
  • 1Department of Neuropsychiatry, College of Medicine, Yeungnam University, Taegu, Korea.
  • 2Department of Pharmacology, College of Medicine, Yeungnam University, Taegu, Korea.
  • 3Department of Neuropsychiatry, Waegwan Hospital, Waegwan, Korea.

Abstract

OBJECTIVES: Pregnanolone is a potent positive modulator of the gamma-aminobutyric acid(GABA) response that enhances the binding of [3H]flunitrazepam to the GABA A receptor. Recently, it was reported that chronic treatment with pregnanolone uncouples allosteric interactions between steroid and benzodiazepine recognition sites. The present study was designed to assess the effect of repeated stress on the modulation of neuroactive steroids on the GABA A receptor.
METHODS
The effect of steroids on the ligands binding to GABA A receptor was investigated using cerebral cortices of unstressed and repeatedly immobilized rats. Male Sprague-Dawley rats, weighing 200-250g were forced to suffer an immobilization stress for 2 hours.
RESULTS
Pregnanolone enhanced the binding of [3H]flunitrazepam to GABA A receptor in both of unstressed and repeatedly stressed rats. However, repeatedly stressed rats showed significantly higher values in EC50 and lower values in E max of enhancement binding of [3H]flunitrazepam than those of unstressed rats.
CONCLUSIONS
From these findings, it can be concluded that repeated stress reduced the positive modulation of neuroactive steroid on the GABA A-receptor complex.

Keyword

Repeated stress; Neuroactive steroid; GABA A-receptor complex
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