PT  - JOURNAL ARTICLE
AU  - David C. Perry
AU  - Danyan Mao
AU  - Allison B. Gold
AU  - J. Michael McIntosh
AU  - John C. Pezzullo
AU  - Kenneth J. Kellar
TI  - Chronic Nicotine Differentially Regulates α6- and β3-Containing Nicotinic Cholinergic Receptors in Rat Brain
AID  - 10.1124/jpet.107.121228
DP  - 2007 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 306--315
VI  - 322
IP  - 1
4099  - http://jpet.aspetjournals.org/content/322/1/306.short
4100  - http://jpet.aspetjournals.org/content/322/1/306.full
SO  - J Pharmacol Exp Ther2007 Jul 01; 322
AB  - We investigated the effects of chronic nicotine on α6- and β3-containing nicotinic acetylcholine receptors (nAChRs) in two rat brain regions using three methodological approaches: radioligand binding, immunoprecipitation, and nicotine-stimulated synaptosomal release of dopamine. Nicotine was administered by osmotic minipumps for 2 weeks. Quantitative autoradiography with [125I]α-conotoxin MII to selectively label α6* nAChRs showed a 28% decrease in binding in the striatum but no change in the superior colliculus. Immunoprecipitation of nAChRs labeled by [3H]epibatidine in these two regions showed that chronic nicotine increased α4- and β2-containing nAChRs by 39 to 67%. In contrast, chronic nicotine caused a 39% decrease in α6-containing nAChRs in striatum but no change in superior colliculus. No changes in β3-containing nAChRs were seen in either region after chronic nicotine. The decreased expression of α6-containing nAChRs persisted for at least 3 days, recovering to baseline by 7 days after removal of the pumps. There was a small but significant decrease in total nicotine-stimulated dopamine release in striatal synaptosomes after nicotine exposure. However, the component of dopamine release that was resistant to α-conotoxin MII blockade was unaffected, whereas dopamine release that was sensitive to blockade by α-conotoxin MII was decreased by 56%. These findings indicate that the α6* nAChR is regulated differently from other nAChR subtypes, and they suggest that the inclusion of a β3 subunit with α6 may serve to inhibit nicotine-induced down-regulation of these receptors. The American Society for Pharmacology and Experimental Therapeutics