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Titolo:
Temporal and regional regulation of alpha 1, beta 2 AND beta 3, but not alpha 2, alpha 4, alpha 5, alpha 6, beta 1 or gamma 2 GABA(A) receptor subunit messenger rnas following one-week oral flurazepam administration
Autore:
Tietz, EI; Huang, X; Chen, S; Ferencak, WF;
Indirizzi:
Med Coll Ohio, Dept Pharmacol, Toledo, OH 43614 USA Med Coll Ohio Toledo OH USA 43614 o, Dept Pharmacol, Toledo, OH 43614 USA
Titolo Testata:
NEUROSCIENCE
fascicolo: 1, volume: 91, anno: 1999,
pagine: 327 - 341
SICI:
0306-4522(1999)91:1<327:TARROA>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
INHIBITORY POSTSYNAPTIC POTENTIALS; CHRONIC BENZODIAZEPINE TREATMENT; AMINOBUTYRIC ACID(A) RECEPTORS; RAT HIPPOCAMPAL-NEURONS; A RECEPTOR; DOWN-REGULATION; GABA(A)-RECEPTOR SUBTYPES; CA1 REGION; FUNCTIONAL EXPRESSION; TREATED RATS;
Keywords:
benzodiazepines; GABA; hippocampus; dependence; tolerance; in situ hybridization;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
85
Recensione:
Indirizzi per estratti:
Indirizzo: Tietz, EI Med Coll Ohio, Dept Pharmacol, 3035 Arlington Ave, Toledo, OH 43614 USA Med Coll Ohio 3035 Arlington Ave Toledo OH USA 43614 H 43614 USA
Citazione:
E.I. Tietz et al., "Temporal and regional regulation of alpha 1, beta 2 AND beta 3, but not alpha 2, alpha 4, alpha 5, alpha 6, beta 1 or gamma 2 GABA(A) receptor subunit messenger rnas following one-week oral flurazepam administration", NEUROSCIENC, 91(1), 1999, pp. 327-341

Abstract

The effect of prolonged benzodiazepine administration on GABA(A) receptor subunit (alpha 1-6, beta 1-3, gamma 2) messenger RNAs was investigated in the rat hippocampus and cortex, among other brain areas. Rats were orally administered flurazepam for one week, a protocol which results in benzodiazepine anticonvulsant tolerance in vivo, and in the hippocampus in vitro, in the absence of behavioral signs of withdrawal. Autoradiographs of brain sections, hybridized with [S-35]oligoprobes in situ, were examined immediately (day 0) or two days after drug treatment, when rats were tolerant, or sevendays after treatment, when tolerance had reversed, and were compared to sections from pair-handled, vehicle-treated controls, al subunit messenger RNA level was significantly decreased in CA1 pyramidal cells and dentate granule cells at day 0, an effect which persisted only in CA1 neurons. Decreased "alpha 1-specific" silver grain density over a subclass of interneurons at the pyramidal cell border suggested concomitant regulation of interneuronGABA(A) receptors. A reduction in beta 3 subunit messenger RNA levels was more widespread among hippocampal cell groups (CA1, CA2, CA3 and dentate gyrus), immediately and two days after treatment, and was also detected in the frontal and parieto-occipital cortices. Changes in beta 2 subunit messenger RNA levels in CA1, CA3 and dentate gyrus cells two days after ending flurazepam treatment suggested a concomitant up-regulation of beta 2 messengerRNA. There was a trend toward an increased level of alpha 5, beta 3 and gamma 2 subunit messenger RNAs in CA1, CA3 and dentate gyrus cells, which wassignificant for the beta 3 and gamma 2 subunit messenger RNAs in the frontal cortex seven days after ending flurazepam treatment. There were no flurazepam treatment-induced changes in any other GABA(A) receptor subunit messenger RNAs. The messenger RNA levels of three (alpha 1, beta 2 and beta 3) of nine GABA(A) receptor subunits were discretely regulated as a function oftime after ending one-week flurazepam treatment related to the presence ofanticonvulsant tolerance, but not dependence. The findings suggested that a localized switch in the subunit composition of GABA(A) receptor subtypes involving these specific subunits may represent a minimal requirement for the changes in GABA(A) receptor-mediated function recorded previously at hippocampal CA1 GABAergic synapses, associated with benzodiazepine anticonvulsant tolerance. (C) 1999 IBRO. Published by Elsevier Science Ltd.

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Documento generato il 07/04/20 alle ore 23:15:20