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Benzodiazepine dependence: from neural circuits to gene expression
J A Pratt1, R R Brett, D J Laurie
1Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, UK.
Pharmacology, Biochemistry, and Behavior
|May 20, 1998
Summary
Benzodiazepine dependence involves brain changes during tolerance and withdrawal. The Papez circuit is key in these processes, suggesting common adaptive mechanisms beyond GABA(A) receptors.
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Benzodiazepine dependence mechanisms are unclear.
- Understanding neural systems in diazepam tolerance and withdrawal is crucial.
- GABA(A) receptor properties may be involved.
Purpose of the Study:
- Test if similar neural systems are involved in diazepam tolerance and withdrawal.
- Investigate associations with GABA(A) receptor changes.
- Map brain structures affected by chronic diazepam and withdrawal.
Main Methods:
- Used 2-deoxyglucose quantitative autoradiography in rats.
- Administered diazepam (5 mg/kg daily) chronically.
- Precipitated withdrawal using flumazenil.
Main Results:
- Diazepam initially reduced glucose utilization brain-wide.
- Tolerance developed differentially in sensory and emotional circuits (Papez circuit).
- Withdrawal showed increased glucose use in the Papez circuit, nucleus accumbens, and amygdala.
Conclusions:
- The Papez circuit is central to diazepam tolerance and withdrawal.
- Suggests common adaptive processes in benzodiazepine effects.
- GABA(A) receptor changes are unlikely the sole mechanism; glutamatergic function may play a role.