Chronic diazepam treatment produces regionally specific changes in GABA-stimulated chloride influx.
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 decreased responsiveness to the stimulation of 36Cl- influx by GABA and a corresponding decrease in the ability of flunitrazepam 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 reduction in GABA/benzodiazepine receptor function following chronic benzodiazepine treatment.
Marley
R J
RJ
Yale University School of Medicine, Department of Psychiatry, Abraham Ribicoff Research Facilities, New Haven, CT 06508.
Gallager
D W
DW
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D005445:Flunitrazepam / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D003975:Diazepam