TY - JOUR T1 - A comparative study of the effects of the intravenous self-administration or subcutaneous minipump infusion of nicotine on the expression of brain neuronal nicotinic receptor subtypes JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.110.064071 SP - mol.110.064071 AU - Milena Moretti AU - Manolo Mugnaini AU - Michela Tessari AU - Michele Zoli AU - Annalisa Gaimarri AU - Irene Manfredi AU - Francesco Pistillo AU - Francesco Clementi AU - Cecilia Gotti Y1 - 2010/01/01 UR - http://molpharm.aspetjournals.org/content/early/2010/05/03/mol.110.064071.abstract N2 - Chronic nicotine exposure changes neuronal acetylcholine nicotinic receptor (nAChR) subtype expression in the brains of smokers and experimental animals. The aim of this study was to investigate nicotine-induced changes in nAChR expression in two models commonly used to describe the effects of nicotine in animals: operant (two-lever presses) intravenous selfadministration (SA), and passive subcutaneous nicotine administration via an osmotic minipump (MP). In the MP group, α4β2 nAChRs were up-regulated in all brain regions, α6β2* nAChRs were down-regulated in the nucleus accumbens (NAc) and caudate-putamen (CPu), and α7 nAChRs were up-regulated in the caudal cerebral cortex (CCx); the upregulation of α4β2α5 nAChRs in the CCx was also suggested. In the SA group, α4β2 upregulation was lower and limited to the CCx and NAc; there were no detectable changes in α6β2* or α7 nACRs. In the CCx of the MP rats, there was a close correlation between the increase in α4β2 binding and α4 and β2 subunit levels measured by means of Western blotting, demonstrating that the up-regulation was due to an increase in α4β2 proteins. Western blotting also showed that the increase in the β2 subunit exceeded that of the α4 subunit, suggesting that a change in α4β2 stoichiometry may occur in vivo as has been shown in vitro. These results show that nicotine has an area-specific effect on receptor subtypes, regardless of its administration route, but the effect is quantitatively greater in the case of MP administration.The American Society for Pharmacology and Experimental Therapeutics ER -