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© 1987 American Academy of Neurology Huntington's diseaseIncreased number and altered regulation of benzodiazepine receptor complexes in frontal cerebral cortexDepartments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry and Behivioral Sciences (Drs. Trifiletti, Snowman, Whitehouse, and Snyder), and the Department of Neurology (Drs. Whitehouse and Marcus), The Johns Hopkins University School of Medicine, Baltimore, MD. The properties of benzodiazepine receptors in samples of six areas of cerebral cortex from patients and controls matched with respect to age, sex, and postmortem delay have been studied by in vitro radioligand binding techniques. A statistically significant 30 to 40% increase in the number of benzodiazepine and allosterically linked GABA-A receptors is observed in the midfrontal cortex (A9/A10), but in no other cortical region examined. The degree of enhancement of [3H]diazepam binding by a given dose of GABA or pentobarbital is significantly reduced in Huntington's disease midfrontal cortex. As in the case of receptor number changes, other cortical regions examined show less prominent changes in regulation of benzodiazepine binding by GABA or pentobarbital. Direct identification of the benzodiazepine binding subunit by photoaffinity labeling with [3H]flunitrazepam reveals a single species of apparent molecular weight 51 kD in patients and controls, suggesting that gross changes in structure of the benzodiazepine binding subunit do not account for the observed alterations in benzodiazepine receptor regulation. Address correspondence and reprint requests to Dr. Whitehouse, Department of Neurology, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, OH 44106. Supported by USPHS grants NS-07179, AG-03359, AG-05146, MH-18501, NS-16375, training grant GM-07309 (R.R.T.), and Research Scientist Award DA-00074 (S.H.S.). Received July 3, 1986. Accepted for publication in final form September 25, 1986.
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