PMID: 8972548Dec 1, 1996Paper

Role of GABA-A and mitochondrial diazepam binding inhibitor receptors in the anti-stress activity of neurosteroids in mice

Psychopharmacology
Doodipala Samba Reddy, S K Kulkarni

Abstract

Neuroactive steroidal modulation of immobilization-stress and possible involvement of GABA-A and mitochondrial diazepam binding inhibitor (DBI) receptors (MDR) has been investigated in mice. Immobilization of mice for 2 h induced intense antinociception, anxiety state, and associated with a fall in adrenal ascorbic acid levels. Pretreatment with high dose of progesterone (10 mg/kg), a precursor of neurosteroids, significantly decreased the stress-induced antinociception, anxiety and fall in adrenal ascorbic acid, while low doses (1 and 5 mg/kg) or hydrocortisone (10 and 100 mg/kg) were ineffective. In contrast, progesterone (1 mg/kg, for 9 days) produced a significant antistress effect, which was blocked by GABA-A antagonists picrotoxin (1 mg/kg) and bicuculline (1 mg/kg), but not by flumazenil (2 mg/kg), a specific benzodiazepine (BZD) antagonist. 4'-chlordiazepam (0.1 and 0.25 mg/kg), a specific high affinity MDR agonist, produced significant anti-stress effect in a flumazenil-insensitive manner, but was blocked by pretreatment with PK11195 (1.5 mg/kg), a selective partial agonist of MDR, and with bicuculline (1 mg/kg), a potent GABA-A receptor antagonist. At higher doses, progesterone and 4'-chlordiazepam which are effective...Continue Reading

Citations

May 21, 1998·European Journal of Pharmacology·D S Reddy, S K Kulkarni
Apr 2, 1999·Psychoneuroendocrinology·A Fernández-Guasti, O Picazo
Apr 1, 2009·Journal of Neurotrauma·Susan MarguliesUNKNOWN Combination Therapies for Traumatic Brain Injury Workshop Leaders
Nov 21, 2008·Clinical and Experimental Pharmacology & Physiology·Hua-Li LiHua Zhao
Sep 19, 2009·Journal of Nutritional Science and Vitaminology·Wenjun ZhouHidehiko Yokogoshi
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Jan 19, 2008·Pharmacology, Biochemistry, and Behavior·Atsuko Kita, Kiyoshi Furukawa
Dec 25, 2004·Neuropharmacology·Doodipala S ReddyMichael A Rogawski
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Jul 11, 2009·Expert Review of Neurotherapeutics·Shrinivas K Kulkarni, Ashish Dhir
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Mar 19, 2015·The Journal of Pharmacology and Experimental Therapeutics·Sandesh D ReddyDoodipala Samba Reddy
Feb 8, 2021·Behavioural Brain Research·Randhall B CarteriLuis Valmor Portela

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