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Chronic exposure to flumazenil: anxiolytic effect and increased exploratory behavior
M Urbancic1, M A Gadek, T J Marczynski
1Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
Pharmacology, Biochemistry, and Behavior
|March 1, 1990
Summary
Chronic flumazenil exposure in rats enhanced exploratory behavior and produced lasting anxiolytic effects, as evidenced by behavioral tests measuring anxiety and conflict. This benzodiazepine receptor antagonist treatment altered responses to novel stimuli and stressful situations.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Psychopharmacology
Background:
- Benzodiazepines are commonly prescribed for anxiety and insomnia.
- Flumazenil is a selective benzodiazepine receptor antagonist.
- Understanding flumazenil's long-term behavioral effects is crucial for its clinical application.
Purpose of the Study:
- To investigate the behavioral consequences of chronic flumazenil exposure in adult rats.
- To determine the duration of these behavioral changes after drug withdrawal.
Main Methods:
- Adult rats received flumazenil (4 mg/kg/day) in drinking water for 21 days.
- Behavioral assessments included the holeboard test, plus-maze test, and drinking-punishment test.
- Tests were conducted during treatment and at various time points after drug withdrawal.
Main Results:
- Flumazenil-treated rats showed increased exploratory activity in the holeboard test.
- Enhanced exploration of open arms and reduced fecal boli in the plus-maze indicated anxiolytic effects.
- A lasting "anticonflict" effect was observed in the drinking-punishment test up to 6 days post-withdrawal.
Conclusions:
- Chronic flumazenil administration induces persistent alterations in exploratory behavior.
- Flumazenil exhibits a lasting anxiolytic effect, influencing responses to novelty and stress.
- These findings highlight the long-term behavioral impact of benzodiazepine receptor antagonism.