It is currently controversial whether all the brain damage in alcohol abusers in the result of
thiamine deficiency (Wernicke-Korsakoff's disease) or whether, in addition,
alcohol abuse may affect the brain by other mechanisms as well. 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 diseases (including
Wernicke's disease), died in
coma, or had
liver disease, significant brain
atrophy, or
dementia severe enough to require
institutionalization. We found that
muscarinic cholinergic synaptic receptor density determined with [3H] quinuclidinly benzilate was decreased by 40% in homogenates of the tempeoral cortex of 26 alcohol abusers compared with 26 matched nonalcoholic controls. The affinities of the
muscarinic receptors were not significantly different between the two groups. 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 2% of the total variance of
protein concentrations and receptor binding. When patients were excluded or included who had received
cholinergic,
anticholinergic, or
benzodiazepine medications before death, no significant effects on the final results were observed.
Pneumonia, known to be associated with acute
hypoxia, and
chronic obstructive pulmonary disease, known to be associated with chronic
hypoxia, where approximately equally distributed between the two groups and had no significant effects on the results reported here. The loss of
muscarinic and the sparing of
benzodiazepine receptors occurs in the temporal cortex of histologically normal brains in the absence of significant
atrophy and of gross
dementia. This means that these changes are early in the development of an alcohol
encephalopathy. We have previously reported a decrease in both
muscarinic and
benzodiazepine receptor binding in the frontal cortex and a decreasing
muscarinic but not
benzodiazepine receptors in the temporal cortex of alcohol abusers. Taken together, these findings suggest that alcohol neurotoxicity does not simply result in a random loss of neurons and or their associated synapses with their receptors. Instead, different types of receptors, depending upon their location in different brain regions, are specifically affected or spared. This suggests the involvement of region- and receptor-specific mechanisms in chronic alcohol toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)