Journal
NEUROPHARMACOLOGY
Volume 46, Issue 8, Pages 1141-1157Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2004.02.009
Keywords
nicotine epibatidine; nicotinic cholinergic receptors; chronic treatment; acetylcholine; Rb-86(+) efflux
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Funding
- NIDA NIH HHS [DA-14152, DA-00197, DA-03194] Funding Source: Medline
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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.
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