Benzodiazepine binding sites in alcoholic cirrhotics: evidence for gender differences.
Synaptic plasma membranes were prepared from superior frontal gyrus and motor cortex obtained at autopsy from 17 chronic alcoholics not differentiated on thiamine status, of whom 8 had pathologically confirmed cirrhosis of the liver, and 10 controls. Three of the cirrhotic alcoholic cases were female, as was one control. Cases were closely matched for age at death and post-mortem delay. The affinity of "central-type" benzodiazepine sites for [3H]diazepam tended to be lower in both brain regions of both groups of alcoholics of cf controls, but the reverse was true for [3H]flunitrazepam, especially in cirrhotic cases. [3H]Diazepam affinity was invariant across all males and the female control, but lower in the female cirrhotic alcoholics. Affinity for [3H]flunitrazepam tended to be the reverse of that for [3H]diazepam. [3H]Diazepam Bmax was markedly lower in female cirrhotic alcoholics, especially in superior frontal gyrus, whereas this region showed a much higher Bmax in the female control case. A small regional difference in [3H]flunitrazepam Bmax was the reverse of that for [3H]diazepam Bmax and was seen in all groups. GABA-mediated neurotransmission may be selectively altered in a pathologically abnormal region of cerebral cortex in cirrhotic alcoholics, and the sexes may show differing susceptibilities to change.
Dodd
P R
PR
Clinical Research Laboratory, Royal Brisbane Hospital Foundation, Bancroft Centre, Australia.
D000328:Adult; D000368:Aged; D001344:Autopsy; D003975:Diazepam / Q000378:metabolism; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000378:metabolism*; D012737:Sex Factors
D011963:Receptors, GABA-A; D005445:Flunitrazepam; D003975:Diazepam