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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1995-11-29
|
| pubmed:abstractText |
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 (GABAA)-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 GABAA 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 GABAA-gated current. Withdrawal from 500 micrograms P administered concomitantly with 2 micrograms 17 beta-estradiol also markedly diminished LZM potentiation of GABAA current. This effect was seen only after three withdrawal cycles. 3. P withdrawal produced no inhibitory effect on either basal levels of GABAA-evoked current, the GABAA EC50, or barbiturate (+/-Pentobarbital, 10(-7)-10(-4) M) modulation of this parameter. 4. The effect of steroid withdrawal on LZM modulation of GABAA-evoked current was blocked by picrotoxin as well as by indomethacin, a drug that prevents conversion of P to its metabolite, the GABAA modulator 3 alpha,5 alpha-THP. These results suggest that the withdrawal properties of P may be due to changes in GABAA receptor function produced by 3 alpha,5 alpha-THP.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzodiazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Chloride Channels,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Modulators,
http://linkedlifedata.com/resource/pubmed/chemical/Lorazepam,
http://linkedlifedata.com/resource/pubmed/chemical/Picrotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/Pregnanolone,
http://linkedlifedata.com/resource/pubmed/chemical/Progesterone,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-3077
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
74
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
464-9
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:7472348-Animals,
pubmed-meshheading:7472348-Benzodiazepines,
pubmed-meshheading:7472348-Brain Chemistry,
pubmed-meshheading:7472348-Chloride Channels,
pubmed-meshheading:7472348-Electrophysiology,
pubmed-meshheading:7472348-Female,
pubmed-meshheading:7472348-GABA Antagonists,
pubmed-meshheading:7472348-GABA Modulators,
pubmed-meshheading:7472348-Hippocampus,
pubmed-meshheading:7472348-Ion Channel Gating,
pubmed-meshheading:7472348-Lorazepam,
pubmed-meshheading:7472348-Picrotoxin,
pubmed-meshheading:7472348-Pregnanolone,
pubmed-meshheading:7472348-Progesterone,
pubmed-meshheading:7472348-Rats,
pubmed-meshheading:7472348-Receptors, GABA-A,
pubmed-meshheading:7472348-Substance Withdrawal Syndrome,
pubmed-meshheading:7472348-gamma-Aminobutyric Acid
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to benzodiazepine modulation in rat CA1 hippocampus.
|
| pubmed:affiliation |
Department of Pharmacology, Zeneca Pharmaceuticals, Wilmington, Delaware 19897, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|