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Evidence for Functional Activity of Up‐Regulated Nicotine Binding Sites in Rat Striatal Synaptosomes
Author(s) -
Rowell Peter P.,
Wonnacott Susan
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb05802.x
Subject(s) - nicotine , dopamine , nicotinic agonist , chemistry , synaptosome , pharmacology , agonist , stimulation , binding site , receptor , endocrinology , medicine , biology , biochemistry , in vitro
A number of studies have found that the chronic administration of nicotine causes an increase in the density of nicotinic binding sites in the brain, but it is not known whether these additional binding sites are functionally active receptors. In this study, the effects of 1‐week administration of the potent nicotinic agonist, (+)‐anatoxin‐a (96 nmol/day via osmotic minipumps), was assessed on [ 3 H]nicotine binding and [ 3 H]dopamine uptake and release in rat striatal synaptosomes. Chronic (+)‐anatoxin‐a treatment resulted in a 32% increase in the B max of [ 3 H]nicotine binding in anatoxin‐treated animals compared to control. There was a 43% increase in the activity of 3 μ M nicotine to release [ 3 H]dopamine from synaptosomes of anatoxin‐treated animals, but the release induced by 20 m M K + depolarization was unaffected. There was no effect of chronic (+)‐anatoxin‐a treatment on the uptake of [ 3 H]dopamine. A strong positive correlation ( r = 0.64) was found between the density of [ 3 H]nicotine binding sites and the nicotine‐induced stimulation of [ 3 H]dopamine release in individual animals. These results indicate that (+)‐anatoxin‐a, like nicotine, produces an up‐regulation of nicotine binding sites following chronic administration, and that these additional sites are functional receptors capable of mediating the release of dopamine from striatal synaptosomes.