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Barbiturate tolerance: effects on GABA-operated chloride channel function.
A M Allan1, X Zhang, L D Baier
1Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110.
Brain Research
|August 21, 1992
Summary
Phenobarbital tolerance reduces its potentiation of GABA-mediated chloride flux and that of benzodiazepines. However, ethanol
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Phenobarbital and benzodiazepines modulate GABA-A receptor activity.
- Understanding drug tolerance mechanisms is crucial for pharmacology.
Purpose of the Study:
- To investigate the effect of phenobarbital tolerance on GABA-mediated chloride flux.
- To explore cross-tolerance between phenobarbital, benzodiazepines, and ethanol at the GABA-A receptor.
Main Methods:
- Inducing phenobarbital tolerance in male ICR mice.
- Assaying brain membrane vesicles (microsacs) for GABA-mediated chloride flux.
- Measuring the potentiation of chloride flux by GABA, phenobarbital, flunitrazepam, ethanol, and FG-7142.
Main Results:
- Phenobarbital tolerance attenuated phenobarbital and flunitrazepam potentiation of GABA-mediated chloride flux.
- Ethanol and FG-7142 modulation of GABA-gated chloride flux remained unaffected by phenobarbital tolerance.
- No significant changes in [3H]diazepam binding parameters were observed.
Conclusions:
- Suggests cross-tolerance between phenobarbital and benzodiazepine agonists at the GABA-A receptor chloride channel.
- Indicates different tolerance mechanisms for ethanol and barbiturates at the GABA-A receptor chloride channel complex.