Interaction of chronic ethanol consumption and aging on brain muscarinic cholinergic receptors

It has been proposed that ethanol and aging may interact synergistically to impair brain function through effects on central muscarinic receptors. Previous studies have investigated the effect of either chronic ethanol treatment or aging, but not both factors simultaneously, on brain muscarinic receptors. We have studied brain muscarinic receptors in animals treated with ethanol for up to 25 months. Ethanol consumption for 3 and 9 months resulted in increased density of quinuclidinyl benzilate (QNB) binding sites in cortex, coinciding with an increase in high-affinity pirenzepine binding sites and low-affinity carbachol binding sites. Upregulation of QNB binding sites in striatum and hippocampus became obvious after further ethanol treatment (15 and 21 months, respectively). Affinity of QNB binding sites and carbachol binding sites was not altered by ethanol treatment. However, there was an ethanol-related decrease in affinity of low-affinity pirenzepine binding sites in cerebral cortex. Density of QNB binding sites and low-affinity pirenzepine binding sites decreased with age in three brain areas investigated. There were age-related changes in receptor affinity in hippocampus and striatum, but not in cortex. Ethanol-related upregulation of muscarinic receptors was superimposed on age-related loss of receptors. We conclude that acceleration of the aging process associated with ethanol abuse is unlikely to be explained on the basis of alterations in receptor density or affinity.