Journal article
WITHDRAWAL FROM THE ENDOGENOUS STEROID PROGESTERONE RESULTS IN GABA(A) CURRENTS INSENSITIVE TO BENZODIAZEPINE MODULATION IN RAT CA1 HIPPOCAMPUS
Journal of neurophysiology, v 74(1), pp 464-469
01 Jul 1995
PMID: 7472348
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
1. The withdrawal properties of the endogenous steroid progesterone (P) were tested in female rats as a function of benzodiazepine modulation of gamma-aminobutyric acid-A (GABA(A))-gated current with the use of the whole cell patch-clamp technique on acutely dissociated CA1 hippocampal neurons. In a previous study, this steroid was shown to exhibit withdrawal properties, behaviorally.
2. One day withdrawal from in vivo administration of physiological doses of P (5 mg ip, 5 days/wk for 3 withdrawal cycles) or its metabolite, the GABA(A) modulator 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP or allopregnanolone, 20 mg/kg ip) prevented the normally potentiating effect of lorazepam (LZM; 10(-7)-10(-4) M) on GABA(A)-gated current. Withdrawal from 500 mu g P administered concomitantly with 2 mu g 17 beta-estradiol also markedly diminished LZM potentiation of GABA(A) current. This effect was seen only after three withdrawal cycles.
3. P withdrawal produced no inhibitory effect on either basal levels of GABA(A)-evoked current, the GABA(A) EC(50), or barbiturate (+/--Pentobarbital, 10(-7)-10(-4) M) modulation of this parameter.
4. The effect of steroid withdrawal on LZM modulation of GABA(A)-evoked current was blocked by picrotoxin as well as by indomethacin, a drug that prevents conversion of P to its metabolite, the GABA(A) modulator 3 alpha,5 alpha-THP. These results suggest that the withdrawal properties of P may be due to changes in GABA(A) receptor function produced by 3 alpha,5 alpha-THP.
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Details
- Title
- WITHDRAWAL FROM THE ENDOGENOUS STEROID PROGESTERONE RESULTS IN GABA(A) CURRENTS INSENSITIVE TO BENZODIAZEPINE MODULATION IN RAT CA1 HIPPOCAMPUS
- Creators
- AMN CostaK T SpenceS S SmithJMH Ffrenchmullen
- Publication Details
- Journal of neurophysiology, v 74(1), pp 464-469
- Publisher
- Amer Physiological Soc
- Number of pages
- 6
- Grant note
- R01 DA-09618-01 / NIDA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) R01DA009618 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:A1995RL65400039
- Scopus ID
- 2-s2.0-0029114495
- Other Identifier
- 991019184307504721
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- Web of Science research areas
- Neurosciences
- Physiology