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)