Subsets of acetylcholine-stimulated 86Rb+ efflux and [125I]-epibatidine binding sites in C57BL/6 mouse brain are differentially affected by chronic nicotine treatment

Nicotinic cholinergic receptor (nAChR) sites that bind nicotine with high affinity (likely alpha4beta2-nAChR) increase following chronic nicotine treatment. Effects of Chronic treatment oil other nAChR binding sites and functional responses of nAChRs are less well studied. Therefore, C57BL/6 mice were intravenously infused for 10 days with saline or nicotine (five doses, 0.25 4.0 mg/kg/h) and nAChR function and three different nicotinic binding sites in 12 brain regions were assessed. Plasma nicotine and cotinine increased linearly with close. Rb-86(+) efflux with higher sensitivity to acetylcholine tended to decrease with increasing dose, whereas efflux with lower sensitivity to acetylcholine tended to increase. As anticipated likely alpha4beta2-nAChR [I-125]-epibatidine binding sites increased with treatment (estimated dosage for one-half maximal increase was 0.44 mg/kg/h, plasma nicotine approximate to20 ng/ml) Rb-86(+) efflux with higher sensitivity to acetylcholine and cytisine-sensitive [I-125]-epibatidine binding are predominantly alpha4beta2-nAChR. A high correlation between these parameters was observed across brain regions and slopes of these regression lines decreased with treatment close, suggesting a decrease in function per unit receptor. Likely alpha3beta4-nAChR binding sites were unaffected even at the highest dose (4.0 mg/kg/h, approximate to210 ng/ml). A third set of diverse nAChR binding sites increased in some brain regions, but only after high-close treatment. (C) 2004 Elsevier Ltd. All rights reserved.