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Titolo:
BLOCKADE OF BEHAVIORAL-EFFECTS OF BRETAZENIL BY FLUMAZENIL AND ZK-93,426 IN PIGEONS
Autore:
WITKIN JM; ACRI JB; GLEESON S; BARRETT EJ;
Indirizzi:
NIDA,ADDICT RES CTR,DRUG DEV GRP,NIH,POB 5180 BALTIMORE MD 21224 UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT BETHESDA MD 20814
Titolo Testata:
Pharmacology, biochemistry and behavior
fascicolo: 1, volume: 56, anno: 1997,
pagine: 1 - 7
SICI:
0091-3057(1997)56:1<1:BOBOBB>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
BENZODIAZEPINE-RECEPTOR ANTAGONIST; DISCRIMINATIVE STIMULUS PROPERTIES; AMINOBUTYRIC ACID(A) RECEPTOR; GABA-A RECEPTORS; RO 15-1788; DRUG DISCRIMINATION; PARTIAL AGONISTS; PENTYLENETETRAZOLE-CUE; INTRINSIC EFFICACIES; DIAZEPAM;
Keywords:
BRETAZENIL; FLUMAZENIL; ZK 93,426; MIDAZOLAM; PUNISHED BEHAVIOR; DRUG DISCRIMINATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
56
Recensione:
Indirizzi per estratti:
Citazione:
J.M. Witkin et al., "BLOCKADE OF BEHAVIORAL-EFFECTS OF BRETAZENIL BY FLUMAZENIL AND ZK-93,426 IN PIGEONS", Pharmacology, biochemistry and behavior, 56(1), 1997, pp. 1-7

Abstract

Benzodiazepine receptor partial agonists manifest full efficacy in preclinical tests of anxiolytic drug action but do not fully reproduce the discriminative stimulus effects of benzodiazepine receptor full agonists in pigeons. The partial agonist, bretazenil, binds to both diazepam-sensitive and diazepam-insensitive GABA(A) receptors. Previous studies have suggested a role for each of these receptor populations in some behavioral effects of bretazenil in pigeons. A possible role for these receptor subtypes in the behavioral effects of bretazenil was further investigated through drug interaction studies with the benzodiazepine receptor antagonists, flumazenil and ZK 93,426. Whereas flumazenil binds with high affinity to both receptor isoforms, ZK 93,426 binds preferentially to diazepam-sensitive binding sites. Bretazenil markedly increased punished responding of pigeons without significantly affecting nonpunished responding. In pigeons discriminating the full benzodiazepine receptor agonist, midazolam, from saline, bretazenil producedonly 60-75% maximal effect. Flumazenil and ZK 93,426 neither increased punished responding nor substituted for midazolam, but hose-dependently blocked the effects of bretazenil on punished responding. Flumazenil also dose-dependently blocked the effects of bretazenil in midazolam-discriminating pigeons, whereas ZK 93,426 only attenuated this effect. These results indicate that bretazenil's actions as a partial agonist at diazepam-sensitive benzodiazepine receptors mediate increases inunished responding and substitution for the discriminiative stimulus effects of midazolam in pigeons. The differences in the effects of flumazenil and ZK 93,426 on the discriminative stimulus effects of bretazenil suggest a potential contribution of diazepam-insensitive sites tothis behavioral effect. Copyright (C) 1997 Elsevier Science Inc.

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Documento generato il 02/04/20 alle ore 18:14:50