AGE-RELATED-CHANGES IN NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR SUBUNIT ALPHA-4 EXPRESSION ARE MODIFIED BY LONG-TERM NICOTINE ADMINISTRATION

The distribution of the neuronal nicotinic acetylcholine receptor subu nit alpha 4 (nAChR alpha 4) in the brains of young (2-4 months) or age d (24-28 months) CBA/J mice was examined using immunohistochemical sta ining. Anti-nAChR alpha 4 immunoreactivity corresponded with nAChR alp ha 4 RNA expression and high-affinity [H-3]nicotine binding. Immunosta ining in aged mice relative to that in young animals was diminished in the medial septum and diagonal band but was unchanged in the globus p allidus and substantia nigra. The staining of neurons was almost compl etely absent in the hippocampus of aged animals. The oral administrati on of nicotine to aged animals for 6 weeks did not alter nAChR alpha 4 expression relative to that in aged controls. However, the long-term delivery of nicotine (11 months) to 14-month-old animals corresponded with the highly specific preservation of nAChR alpha 4 expression in s ome neurons of the dentate gyrus region and in neurite processes of re maining neurons of the hippocampal CA1 region. These results support t he conclusion that the loss of nAChR alpha 4 expression occurs in key cholinergic regions during normal aging. Furthermore, sustained long-t erm nicotine delivery may promote highly region-specific retention of nAChR expression, but only if initiated before normal age-related rece ptor decline.