Chronic diazepam treatment produces regionally specific changes in GABA-stimulated chloride influx

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Abstract

GABA-stimulated 36Cl influx was used to investigate regional differences in response to chronic diazepam treatment by comparing cortical and cerebellar tissue from rats chronically treated with diazepam for 3 weeks. Using a treatment protocol which has previously been shown to produce behavioral tolerance and physical dependence, cortical membrane preparations from chronic diazepam-treated rats were found to exhibit a decrease in the ability of flunitrazepam to enhance to the stimulation of 36Cl influx. This decrease in sensitivity to enhance GABA-stimulated 36Cl influx. This decrease in sensitivity to flunitrazepam, however, appears to reflect the underlying decrease in sensitivity to GABA. In contrast, in membrane vesicles prepared from cerebella of chronic diazepam-treated rats, there was no measurable effect on GABA-stimulated 36Cl-influx or on the enhancement of GABA-stimulated 36Cl influx by flunitrazepam. These results support the suggestion that there is a regionally specific specific reduction in GABA/benzodiazepine receptor function following chronic benzodiazepine treatment.

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