RATIONALE: Flumazenil, a competitive antagonist of benzodiazepine receptors (BZRs), has been used as a probe to detect effects of putative endogenous ligands for BZRs in anxiety. Flumazenil is renowned for its highly inconsistent behavioral effects. OBJECTIVE: To ascertain effects of flumazenil in the social conflict test in mice, which provides complex measures for prediction of anxiolytic and anxiogenic activity of drugs in behaviorally different groups of animals. METHODS: Singly housed male mice treated with flumazenil (5, 20 or 80 mg/kg i.p.) or vehicle were paired with untreated non-aggressive group-housed male mice in a novel cage. Behavior was analyzed from video tapes of the social interactions in three populations of mice: timid (n=21), aggressive (n=11), and sociable (n=7). Levels of gamma-aminobutyric acid (GABA) were measured in vivo in the prefrontal cortex. RESULTS: Flumazenil reduced timid (defensive-escape) and increased locomotor activities in timid mice. The drug reduced aggressive and increased sociable (social investigation) activities in aggressive mice. These behavioral changes were produced at the lowest dose of flumazenil tested (5 mg/kg) and were not increased further by higher doses of the drug (20 mg/kg or 80 mg/kg). A tendency to increased timidity was found after flumazenil in sociable mice. Concentrations of GABA were markedly higher in the prefrontal cortex of sociable mice than in timid or aggressive mice. CONCLUSIONS: Flumazenil produced moderate anxiolytic-like behavioural changes and a slight anxiogenic-like effect. The present data might be reflecting antagonism of corresponding endogenous BZR ligands. However, these putative ligands seem to exert only modest modulatory influence.

• MeSH
• agrese účinky léků   fyziologie   MeSH
• flumazenil farmakologie   MeSH
• konflikt (psychologie) * MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   fyziologie   MeSH
• sociální chování * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• flumazenil MeSH

The effects were ascertained of two partial inverse agonists at benzodiazepine receptors (beta-CCE and FG 7142) on the incidence of timid (defensive-escape), aggressive, sociable and locomotor activities in both timid and aggressive singly-housed male mice, treated with drugs in paired interactions with untreated non-aggressive males. FG 7142 (5 mg/kg) and beta-CCE (8 mg/kg) increased defenses and escapes without producing other behavioral changes in timid mice. FG 7142 (20 mg/kg) and beta-CCE (1-8 mg/kg) moderately increased defenses and alert postures in aggressive mice and this effect was associated with marked reduction of aggressive behavior. FG 7142 (20 and 80 mg/kg) also decreased walking across cage in aggressive mice. It is concluded that beta-CCE and FG 7142 produced behavioral changes which could be interpreted as "anxiogenic".

• MeSH
• agrese účinky léků   MeSH
• antagonisté receptorů GABA-A * MeSH
• interpersonální vztahy MeSH
• karboliny farmakologie   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pohybová aktivita účinky léků   MeSH
• úniková reakce účinky léků   MeSH
• úzkost chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté receptorů GABA-A * MeSH
• beta-carboline-3-carboxylic acid ethyl ester MeSH Prohlížeč
• FG 7142 MeSH Prohlížeč
• karboliny MeSH