Decline in response to nicotine in aged rat striatum: correlation with a decrease in a subpopulation of nicotinic receptors.
Specific and reproducible changes involving the cholinergic and dopaminergic systems have been described in both the aging rodent and the human nervous system. Nevertheless, relatively little information is available on changes in nicotinic cholinergic receptors occurring in normal aging, and there have been few attempts to correlate alterations in receptor densities with changes in nicotinic actions. We have utilized the nicotine-mediated stimulation of endogenous dopamine efflux in a striatal slice preparation as a functional index of responsiveness to nicotine in aging. Following incubation with nicotine, this efflux was significantly lower in 25-month-old (aged) as opposed to 4-month-old (young) rats. In contrast, the release of striatal dopamine following a high-potassium stimulus was similar at both ages. Binding studies in young and aged animals did not reveal any significant change with age in the total number of striatal nicotinic receptors recognized by either [3H]nicotine or the neuronal nicotinic antagonist 125I-neuronal bungarotoxin. However, there was a nearly 80% decline in the subpopulation of striatal nicotinic receptors jointly recognized by both nicotine and neuronal bungarotoxin, but not by alpha-bungarotoxin. Quantitative autoradiography demonstrated declines with age in this receptor subtype in several brain regions examined. Decrements in this specific subpopulation of nicotinic receptors or in the nerve cells expressing these receptors may contribute to the functional declines that take place in the aging motor and visual systems.
Schulz
D W
DW
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
Kuchel
G A
GA
Zigmond
R E
RE
D000375:Aging / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D009538:Nicotine / Q000494:pharmacology*; D009928:Organ Specificity; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014316:Tritium
D007457:Iodine Radioisotopes; D011978:Receptors, Nicotinic; D014316:Tritium; D009538:Nicotine; D011188:Potassium; D004298:Dopamine