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Titolo:
PHARMACOLOGICAL ACTIONS OF SUBTYPE-SELECTIVE AND NOVEL GABAERGIC LIGANDS IN RAT LINES WITH DIFFERENTIAL SENSITIVITY TO ETHANOL
Autore:
WONG G; SARVIHARJU M; TOROPAINEN M; MATECKA D; KORPI ER;
Indirizzi:
ALKO GRP LTD,BIOMED RES CTR,POB 350 SF-00101 HELSINKI FINLAND ALKO GRP LTD,BIOMED RES CTR SF-00101 HELSINKI FINLAND NIDDKD,NIH,MED CHEM LAB BETHESDA MD 20892
Titolo Testata:
Pharmacology, biochemistry and behavior
fascicolo: 3, volume: 53, anno: 1996,
pagine: 723 - 730
SICI:
0091-3057(1996)53:3<723:PAOSAN>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
INSENSITIVE BENZODIAZEPINE RECEPTORS; GABA-A RECEPTORS; INDUCED MOTOR IMPAIRMENT; LOW ALCOHOL SENSITIVITY; )H-3>RO 15-4513; PARTIAL AGONIST; BINDING-SITES; DIAZEPAM; LORECLEZOLE; ZOLPIDEM;
Keywords:
ALCOHOL SENSITIVITY; BENZODIAZEPINE RECEPTORS; GABA(A) RECEPTOR SUBTYPES; ZOLPIDEM; BRETAZENIL ZG-63; LORECLEZOLE; SELECTED RAT LINES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
G. Wong et al., "PHARMACOLOGICAL ACTIONS OF SUBTYPE-SELECTIVE AND NOVEL GABAERGIC LIGANDS IN RAT LINES WITH DIFFERENTIAL SENSITIVITY TO ETHANOL", Pharmacology, biochemistry and behavior, 53(3), 1996, pp. 723-730

Abstract

Alcohol-nontolerant (ANT) rats, produced by selective breeding for high sensitivity to motor-impairing effects of ethanol, have a point mutation in the cerebellar gamma-aminobutyric acid type A (GABA(A)) receptor alpha 6 subunit, which has been proposed to underlie enhanced sensitivity to benzodiazepine agonists as well. We compared ANT and alcohol-tolerant (AT) rats using behavioral and neurochemical methods to assess the significance of alpha 6- and non alpha 6-containing GABA(A) receptor subtypes. Motor performance in a tilting plane test was largelyunaffected by a type I benzodiazepine receptor-preferring agonist, zolpidem [1-10 mg/kg, intraperitoneally (IP)], partial benzodiazepine agonists bretazenil and ZG-63 (both at 40 mg/kg, IF), and a novel broad-spectrum anticonvulsant loreclezole (40 mg/kg, IF) in both ANT and AT rats. In contrast, diazepam (10 mg/kg, IF) impaired performance of theANT but not AT animals. These data, supported by results from blain regional autoradiography of [H-3]Ro15-4513 and membrane binding of [H-3]ZG-63 and [S-35]TBPS as influenced by these ligands, strongly suggestthat only ligands with full agonist actions on mutant (ANT) but not wild-type (AT) alpha 6-containing GABA(A) receptors are able to producemotor impairment in the ANT rats.

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Documento generato il 09/04/20 alle ore 19:14:15