Loss of muscarinic and benzodiazepine neuroreceptors from hippocampus of alcohol abusers.
Thiamine deficiency (Wernicke-Korsakoff's disease) may not be the only mechanism whereby chronic alcohol abuse affects the brain and not all alcohol-related changes may be evident morphologically. The purpose of this study was to determine if alcohol abuse affects muscarinic cholinergic and benzodiazepine receptors in the hippocampus of histologically normal brains obtained at autopsy in a general hospital population. Because patients were excluded who had significant brain atrophy and/or dementia severe enough to require institutionalization, the reported findings are presumed to be early changes in the development of an alcohol encephalopathy. In addition, patients were excluded from this study if they had clinical brain diseases (including Wernicke's disease), died in coma, had liver disease, or received medications that could potentially alter receptor binding. The reported changes in receptor binding were therefore presumed to be related to alcohol abuse per se and not an alcohol-associated condition. We found that muscarinic cholinergic synaptic receptor density determined with 3[H] quinuclidinyl benzilate was decreased by 30% in homogenates of the hippocampus of 25 alcohol abusers compared with 25 matched nonalcoholic controls. Similarly, densities of benzodiazepine receptors determined with 3[H] flunitrazepam were also decreased by approximately 30% in alcohol abusers. The affinities of both receptor types were not affected by alcohol abuse. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Freund
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Medical Service Veterans Administration Medical Center, Gainesville, FL 32602.
Ballinger
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D000375:Aging / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D001667:Binding, Competitive; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate; D011963:Receptors, GABA-A / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D005445:Flunitrazepam; D011813:Quinuclidinyl Benzilate