The Effect of Repeated Stress on the Modulation of Neuroactive Steroids at the GABAA-Benzodiazepine Receptor Complex in Rats.
- Author:
Bong Suk JANG
1
;
Jong Bum LEE
;
Hyung Bae PARK
;
Jung Hee HA
;
Chang Jin SONG
Author Information
1. Department of Neuropsychiatry, College of Medicine, Yeungnam University, Taegu, Korea.
- Publication Type:Original Article
- Keywords:
Repeated stress;
Neuroactive steroid;
GABA A-receptor complex
- MeSH:
Animals;
Benzodiazepines;
Cerebral Cortex;
gamma-Aminobutyric Acid;
Humans;
Immobilization;
Ligands;
Male;
Pregnanolone;
Rats*;
Rats, Sprague-Dawley;
Receptors, GABA-A;
Steroids*
- From:Journal of Korean Neuropsychiatric Association
1999;38(3):656-663
- CountryRepublic of Korea
- Language:Korean
-
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.
