Autoradiographic localization of benzodiazepine receptor downregulation
Regional differences in downregulation of brain benzodiazepine receptors were studied using a quantitative autoradiographic method. Rats were given a 4-week flurazepam treatment known to cause tolerance and receptor downregulation. A second group of rats was given a similar treatment, but for only 1 week. A third group was given a single acute dose of diazepam to produce a brain benzodiazepine-like activity equivalent to that found after the chronic treatment. Areas studied included hippocampal formation, cerebral cortex, superior colliculus, substantia nigra, dorsal geniculate nucleus, lateral amygdala and lateral hypothalamus. There was a regional variation in the degree of downregulation after 1 week of flurazepam treatment, ranging from 12% to 25%. Extending the flurazepam treatment to 4 weeks caused little further downregulation in those areas studied, except for the pars reticulata of the substantia nigra, which showed a 13% reduction in (/sup 3/H)flunitrazepam binding after 1 week and a 40% reduction after 4 weeks of treatment. In a few areas, such as the lateral hypothalamus, no significant change in binding was found after 4 weeks. Acute diazepam treatment caused no change in binding. This latter finding as well as results obtained during the development of the methodology show that downregulation was not an artifact due to residual drug content of brain slices. The regional variations in degree and rate of downregulation suggest areas that may be most important for benzodiazepine tolerance and dependence and may be related to the varying time courses for tolerance to different benzodiazepine actions.
- Research Organization:
- Medical College of Ohio, Toledo
- OSTI ID:
- 5811173
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 1
- Country of Publication:
- United States
- Language:
- English
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BRAIN
AUTORADIOGRAPHY
RECEPTORS
DRUGS
HYPOTHALAMUS
IN VITRO
RATS
TRITIUM COMPOUNDS
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CENTRAL NERVOUS SYSTEM
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
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ORGANIC COMPOUNDS
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550201* - Biochemistry- Tracer Techniques