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Alterations in GABAergic function following forced swimming stress
Alfredo Briones-Aranda1, Luisa Rocha, Ofir Picazo
1Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Diaz Mirón, Col. Sto. Tomás, 11340 México City, México.
Pharmacology, Biochemistry, and Behavior
|March 3, 2005
Summary
Forced swimming stress significantly reduces the anti-anxiety effects of diazepam in mice. This stress response impacts GABA levels and receptor sensitivity, diminishing the drug's efficacy in managing anxiety.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Forced swimming is a known stressor that alters brain chemistry.
- Stress can impact the efficacy of anxiolytic medications like benzodiazepines.
- Allopregnanolone release during stress may influence GABA/benzodiazepine receptor function.
Purpose of the Study:
- To investigate if forced swimming stress modifies the anti-anxiety effects of diazepam.
- To explore the relationship between stress-induced changes in allopregnanolone, GABA concentration, and GABA/benzodiazepine receptor density.
- To determine the impact of stress on diazepam's anxiolytic action.
Main Methods:
- Mice were subjected to forced swimming stress or kept unstressed.
- Animals received vehicle or diazepam injections.
- Exploratory behavior tests were used to assess anxiety levels.
- GABA concentrations and benzodiazepine receptor density were measured.
Main Results:
- Diazepam demonstrated anxiolytic effects in unstressed mice but not in stressed mice.
- Allopregnanolone administration blocked diazepam's anxiolytic effect in stressed animals.
- Forced swimming reduced GABA concentrations in the hippocampus and thalamus-hypothalamus.
- Stress decreased [(3)H]flunitrazepam labeling in the hypothalamus and amygdala.
Conclusions:
- Forced swimming stress abolishes the anti-anxiety effect of diazepam.
- Stress-induced alterations in GABAergic neurotransmission and receptor binding contribute to the diminished efficacy of diazepam.
- Allopregnanolone plays a role in mediating the stress-induced reduction in diazepam's anxiolytic properties.