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In vitro studies on GABA release.
British Journal of Clinical Pharmacology
|January 1, 1979
Summary
Benzodiazepines, like diazepam and clobazam, reduce the release of gamma-aminobutyric acid (GABA) in the brain. This effect, observed in rat brain cortex slices, suggests a feedback mechanism regulating neurotransmission.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Benzodiazepines are known to interact with GABAergic systems.
- Previous research suggested benzodiazepines facilitate GABA-mediated neurotransmission, possibly by enhancing GABA release.
Purpose of the Study:
- To investigate the effect of benzodiazepines (diazepam, clobazam) and other psychotropic drugs on stimulated GABA release.
- To explore the mechanism underlying benzodiazepine action on GABAergic neurotransmission.
Main Methods:
- Experiments utilized rat brain cortex slices pre-loaded with [3H]-GABA.
- Electrically stimulated overflow of GABA was measured in the presence and absence of drugs.
- The role of GABA receptors was assessed using the antagonist bicuculline.
Main Results:
- Diazepam and clobazam significantly reduced stimulated GABA release in a concentration-dependent manner.
- This reduction was antagonized by bicuculline, indicating involvement of GABA receptors.
- Other drugs like hexobarbitone and cyclic GMP also showed a reduction in GABA release, though less pronounced.
Conclusions:
- Benzodiazepines inhibit, rather than enhance, stimulated GABA release.
- A model of presynaptic GABA autoreceptors is proposed to explain this inhibitory feedback control of GABA release.