α4 but Not α3 and α7 Nicotinic Acetylcholine Receptor Subunits Are Lost from the Temporal Cortex in Alzheimer's Disease

In a postmortem study of nicotinic receptors in human brain, cigarette smoking was found to be associated with increased (-)-[3H]nicotine binding to membranes prepared from gyrus rectus (Brodmann area 11) (p less than 0.001), hippocampal neocortex (Brodmann area 27), cerebellar cortex (p less than 0.01), hippocampal formation (Ammon's horn + subiculum), and the median raphe nuclei of the midbrain (p less than 0.05) but not the medulla oblongata. Analysis of the binding data suggested that the increased binding reflected an increase in the density of the receptors rather than a change in their affinity for (-)-nicotine. The effects of smoking were not influenced significantly by either the sex or age of the subject. It is concluded that smoking evokes an increase in high-affinity nicotine binding similar to that observed previously in animals treated chronically with nicotine and that the effect of smoking on these sites is probably caused by the nicotine present in the tobacco smoke.