Necropsy study of GABA/benzodiazepine receptor binding sites in brain tissue from chronic alcoholic patients.
Neurological and cognitive deficits occur in many chronic alcoholic patients. Quantitative studies reveal a significant reduction in the number of neurons in the superior frontal gyrus of chronic alcoholics, with no change in the motor cortex. Our studies are aimed at delineating which neurotransmitter systems are altered in alcoholics and to correlate these alterations with morphometry and, where possible, clinical signs. Much evidence suggests both short- and long-term effects of ethanol on GABA-mediated neurotransmission. GABA and benzodiazepines bind to distinct, but allosterically linked, sites on the GABA/benzodiazepine receptor complex. In the absence of any detected difference in the number of benzodiazepine receptors in both the frontal and motor cortex from alcoholic and control patients, a significant increase in the amount of GABA enhancement of [3H]diazepam binding was measured in frontal cortex membranes from patients with Wernicke's encephalopathy relative to non-alcoholic controls. This finding suggests an increased coupling of the GABA and benzodiazepine recognition sites in this area, which may be due to ethanol-induced conformational changes in the receptor complex.
Kril
J J
JJ
Department of Pathology, University of Sydney, NSW.
Dodd
P R
PR
Gundlach
A L
AL
Davies
N
N
Watson
W E
WE
Johnston
G A
GA
Harper
C G
CG
D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003975:Diazepam / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism*; D006801:Humans; D011963:Receptors, GABA-A / Q000378:metabolism*
D011963:Receptors, GABA-A; D005445:Flunitrazepam; D003975:Diazepam