Neuroreceptor changes in the putamen of alcohol abusers.
The purpose of this study was to determine if alcohol abuse affects muscarinic cholinergic and benzodiazepine receptors in histologically normal brains obtained at autopsy in a general hospital population. Patients were excluded from this study if they had clinical brain (including Wernicke's) disease, died in coma, had liver disease, significant brain atrophy, or dementia severe enough to require institutionalization. We found that muscarinic cholinergic synaptic receptor density determined with [3H]quinuclidinyl benzilate was decreased by 40% in homogenates of the putamen of 27 alcohol abusers compared with 37 matched nonalcoholic controls. In contrast, receptor densities and affinities of benzodiazepine receptors determined with [3H]flunitrazepam were not significantly different in the two groups. Age and death-autopsy time interval had no significant effects on either wet tissue protein concentrations, yields of protein after centrifugation, or receptor binding. The contributions of age and time interval were each less than 3% of the total variance of protein concentrations and receptor binding. When patients who had received cholinergic, anticholinergic, or benzodiazepine medications before death were excluded or included we observed no significant effects on the final results. Pneumonia, known to be associated with acute hypoxia, and chronic obstructive pulmonary disease, known to be associated with chronic hypoxia, were approximately equally distributed between the two groups and had no significant effects on the results reported here. It is significant that the loss of muscarinic and the sparing of benzodiazepine receptors in the putamen occurs in histologically normal brains in the absence of significant atrophy and gross dementia. It implies that these changes are early in the development of alcoholic encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Freund
G
G
Veterans Administration Medical Center, Gainesville, Florida 32602.
Ballinger
W E
WE
D000328:Adult; D000375:Aging / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D005445:Flunitrazepam / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; D005445:Flunitrazepam; D011813:Quinuclidinyl Benzilate