Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
TOLERANCE TO DIAZEPAM AND CHANGES IN GABA(A) RECEPTOR SUBUNIT EXPRESSION IN RAT NEOCORTICAL AREAS
Autore:
PESOLD C; CARUNCHO HJ; IMPAGNATIELLO F; BERG MJ; FRITSCHY JM; GUIDOTTI A; COSTA E;
Indirizzi:
UNIV ILLINOIS,INST PSYCHIAT,1601 W TAYLOR ST,M-C 912 CHICAGO IL 60612 UNIV ILLINOIS,INST PSYCHIAT CHICAGO IL 60612 UNIV SANTIAGO DE COMPOSTELA,SCH MED,DEPT MORPHOL SCI SANTIAGO COMPOSTE 15705 SPAIN NATHAN S KLINE INST PSYCHIAT RES,CTR NEUROCHEM ORANGEBURG NY 10962 UNIV ZURICH,INST PHARMACOL CH-8057 ZURICH SWITZERLAND
Titolo Testata:
Neuroscience
fascicolo: 2, volume: 79, anno: 1997,
pagine: 477 - 487
SICI:
0306-4522(1997)79:2<477:TTDACI>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITIVE ALLOSTERIC MODULATOR; A BENZODIAZEPINE RECEPTOR; CEREBELLAR GRANULE CELLS; MESSENGER-RNAS; CORTICAL-NEURONS; FLURAZEPAM TREATMENT; MOLECULAR-BIOLOGY; PRIMARY CULTURES; ALPHA-SUBUNITS; BRAIN-REGIONS;
Keywords:
BENZODIAZEPINES; TOLERANCE; GABA(A); RECEPTOR SUBUNITS; DIAZEPAM; IMIDAZENIL; IMMUNOGOLD LABELING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
66
Recensione:
Indirizzi per estratti:
Citazione:
C. Pesold et al., "TOLERANCE TO DIAZEPAM AND CHANGES IN GABA(A) RECEPTOR SUBUNIT EXPRESSION IN RAT NEOCORTICAL AREAS", Neuroscience, 79(2), 1997, pp. 477-487

Abstract

Long-term treatment with diazepam, a full allosteric modulator of theGABA(A) receptor, results in tolerance to its anticonvulsant effects,whereas an equipotent treatment with the partial allosteric modulatorimidazenil does not produce tolerance. Use of subunit-specific antibodies linked to gold particles allowed an immunocytochemical estimationof the expression density of the alpha(1), alpha(2), alpha(3), alpha(5), gamma(2L&S) land beta(2/3) subunits of the GABA(A) receptor in thefrontoparietal motor and frontoparietal somatosensory cortices of rats that received long-term treatment with vehicle, diazepam (three times daily for 14 days, doses increasing from 17.6 to 70.4 mu mol/kg), orimidazenil (three times daily for 14 days, doses increasing from 2.5 to 10.0 mu mol/kg). In this study, tolerance to diazepam was associated with a selective decrease (37%) in the expression of the alpha(1) subunit in layers III-IV of the frontoparietal motor cortex, and a concomitant increase in the expression of the alpha(5) (150%), gamma(2L&S) and beta(2/3) subunits (48%); an increase in alpha(5) subunits was measured in all cortical layers. In the frontoparietal somatosensory cortex, diazepam-tolerant rats had a 221% increase in the expression of alpha(5) subunits in all cortical layers, as well as a 35% increase in the expression of alpha(3) subunits restricted to layers V-VI. Western blot analysis substantiated that these diazepam-induced changes reflected the expression of full subunit molecules. Rats that received equipotent treatment with imidazenil did not become tolerant to its anticonvulsant properties, and did not show significant changes in the expression of any of the GABA(A) receptor subunits studied, with the exception of a small decrease in alpha(2) subunits in cortical layers V-VI ofthe Frontoparietal somatosensory cortex. The results of this study suggest that tolerance to benzodiazepines may be associated with select changes in subunit abundance, leading to the expression of different GABA(A) receptor subtypes in specific brain areas. These changes might he mediated by a unique homeostatic mechanism regulating the expression of GABA(A) receptor subtypes that maintain specific functional features of GABAergic function in cortical cell layers. (C) 1997 IBRO. Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 11:17:30