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Titolo:
Substantia nigra: The involvement of central and peripheral benzodiazepinereceptors in physical dependence on diazepam as evidenced by behavioral and EEG effects
Autore:
Wala, EP; Sloan, JW; Jing, X;
Indirizzi:
Univ Kentucky, Coll Med, Dept Anesthesiol, Res Facil 3, Lexington, KY 40536 USA Univ Kentucky Lexington KY USA 40536 Res Facil 3, Lexington, KY 40536 USA
Titolo Testata:
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
fascicolo: 3, volume: 64, anno: 1999,
pagine: 611 - 623
SICI:
0091-3057(199911)64:3<611:SNTIOC>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
PARS-RETICULATA NEURONS; CENTRAL-NERVOUS-SYSTEM; BINDING-SITES; AUTORADIOGRAPHIC LOCALIZATION; RAT-BRAIN; PHARMACODYNAMIC INTERACTION; PRECIPITATED ABSTINENCE; CHLORIDE IONOPHORE; INTRINSIC EFFICACY; FIRING RATE;
Keywords:
substantia nigra; central benzodiazepine receptor; peripheral benzodiazepine receptors; focal injection; flumazenil; PK 11195; precipitated withdrawal; EEG;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
84
Recensione:
Indirizzi per estratti:
Indirizzo: Wala, EP Univ Kentucky, Coll Med, Dept Anesthesiol, Res Facil 3, Room 209,Limestone& KY Clin Dr, Lexington, KY 40536 USA Univ Kentucky Room 209,Limestone & KY Clin Dr Lexington KY USA 40536
Citazione:
E.P. Wala et al., "Substantia nigra: The involvement of central and peripheral benzodiazepinereceptors in physical dependence on diazepam as evidenced by behavioral and EEG effects", PHARM BIO B, 64(3), 1999, pp. 611-623

Abstract

Male rats chronically exposed to diazepam (DZ) slowly released from subcutaneously implanted silastic capsules along with empty capsule control rats were focally injected (1 mu l) into the substantia nigra (SNR) with the central (CBR) and peripheral (PBR) benzodiazepine receptor antagonists, flumazenil [(FLU) 6.25, 12.5, 25 mu g] and PK 11195 [(PK) 3.125, 6.25, 12.5, 25 mu g] respectively (weekly intervals; Latin square design). Rats were observed for signs of withdrawal and the EEG was recorded simultaneously from thesite of injection (SNR), caudate putamen, thalamus, hippocampus, and frontal cortex. In DZ-dependent rats the Precipitated Abstinence Score (PAS) wassignificantly related to dose of FLU. The PAS increased with increasing doses of PK (3.125-12.5 mu g); however, the highest dose of PK (25 mu g) showed less effect. The rapid onset of the PAS was accompanied by a rise in thetotal power (1-32 Hz) of the EEG (TPEEG) in the SNR and other brain areas. The PAS and TPEEG had similar time courses. Intranigrally injected FLU andPK did not evoke clonic and tonic-clonic convulsions; however, both antagonists induced dose-related twitches and jerks. Additionally, FLU precipitated a dose-related tachypnea and increases in turning and backing. Chronic DZ treatment altered the spectral content of the EEG, as indicated by a decrease and an increase of the slow and fast frequency bands, respectively. FLU and PK rapidly but transiently reversed the EEG. Data suggest that in theSNR the CBR mediate autonomic and motor signs of DZ withdrawal, while boththe CBR and PER are responsible for twitches and jerks and alteration of the EEG. It is possible that PK also acts on the site linked to a GABA(A)/CBR/ionophore. (C) 1999 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 09:36:04