ABSTRACT
Nicotine and nicotinic agonists such as acetylcholine, methylcarbamyl choline, and cytisine at nanomolar concentrations bind to a separate group of central nervous system (CNS) receptors than alpha-bungarotoxin, and recent studies have confirmed different molecular structures for these two groups of receptors. The various alpha subunits are expressed in distinct distribution patterns, and different subunit combinations result in a range of receptor pharmacological profiles. The levels of high-affinity nicotinic binding and expression of corresponding messenger RNAs are highest in the thalamus and other midbrain and brainstem structures and may be associated with brainstem and cholinergic projections. CNS nicotinic receptors are reduced in neuropathological conditions such as Alzheimer’s disease, Parkinson’s disease, and Lewy body dementia as well as in normal aging. The number of these receptors is up-regulated by exposure to some nicotinic agonists and tobacco smoke. In normal human aging, loss of brain high-affinity nicotine binding has been observed in the frontal cortex and hippocampus.
