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Binding and functional activity of nicotinic cholinergic receptors in selected rat brain regions are increased following long‐term but not short‐term nicotine treatment
Author(s) -
Nguyen Henry N.,
Rasmussen Bruce A.,
Perry David C.
Publication year - 2004
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.1471-4159.2004.02482.x
Subject(s) - epibatidine , interpeduncular nucleus , nicotinic agonist , nicotine , chemistry , cholinergic , endocrinology , acetylcholine receptor , medicine , habenula , cytisine , receptor , pharmacology , nicotinic acetylcholine receptor , biology , central nervous system , biochemistry , midbrain
Chronic nicotine exposure up‐regulates neuronal nicotinic receptors, but the functional consequences for these receptors is less well understood. Following 2 weeks of nicotine or saline treatment by osmotic minipump, the functional activity of nicotinic receptors was measured by concentration–response curves for epibatidine‐stimulated 86 Rb efflux. Nicotine‐treated animals had a significantly higher maximal efflux in cerebral cortex and superior colliculus, but not in thalamus or interpeduncular nucleus plus medial habenula. This increase was confirmed in a separate experiment with stimulation by single concentrations of epibatidine (cortex, superior colliculus) or nicotine (cortex only). Chronic nicotine did not alter 86 Rb efflux stimulated by cytisine, an α3β4‐selective agonist, or by potassium chloride, in any region. Short‐term (16 h) nicotine exposure caused no changes in either 86 Rb efflux or receptor binding measured with [ 3 H]epibatidine. Binding was significantly increased after 2 weeks nicotine exposure in cortex, superior colliculus and thalamus, but not in interpeduncular nucleus plus medial habenula. The increases in epibatidine‐stimulated 86 Rb efflux in the four regions tested was linearly correlated with the increases in [ 3 H]epibatidine binding in these regions ( R 2 = 0.91), suggesting that rat brain receptors up‐regulated by chronic nicotine are active. These results have important consequences for understanding nicotinic receptor neurobiology in smokers and users of nicotine replacement therapy.