1. 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
- Author
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Manolo Mugnaini, Cecilia Gotti, Francesco Clementi, Michele Zoli, Annalisa Gaimarri, Francesco Pistillo, Michela Tessari, Milena Moretti, and Irene Manfredi
- Subjects
Male ,Nicotine ,Blotting, Western ,Molecular Sequence Data ,Self Administration ,Pharmacology ,Nucleus accumbens ,Receptors, Nicotinic ,Radioligand Assay ,In vivo ,medicine ,Animals ,Immunoprecipitation ,Amino Acid Sequence ,Receptor ,Infusions, Intravenous ,Neurons ,Chemistry ,Brain ,Rats ,Blot ,medicine.anatomical_structure ,Nicotinic agonist ,Cerebral cortex ,Molecular Medicine ,sense organs ,Self-administration ,medicine.drug ,nicotine ,self-administration ,osmotic minipumps ,nicotinic receptors ,up-regulation - Abstract
Long-term 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 self-administration (SA) and passive subcutaneous nicotine administration via an osmotic minipump (MP). In the MP group, alpha4beta2 nAChRs were up-regulated in all brain regions, alpha6beta2* nAChRs were down-regulated in the nucleus accumbens (NAc) and caudate-putamen, and alpha7 nAChRs were up-regulated in the caudal cerebral cortex (CCx); the up-regulation of alpha4beta2alpha5 nAChRs in the CCx was also suggested. In the SA group, alpha4beta2 up-regulation was lower and limited to the CCx and NAc; there were no detectable changes in alpha6beta2* or alpha7 nACRs. In the CCx of the MP rats, there was a close correlation between the increase in alpha4beta2 binding and alpha4 and beta2 subunit levels measured by means of Western blotting, demonstrating that the up-regulation was due to an increase in alpha4beta2 proteins. Western blotting also showed that the increase in the beta2 subunit exceeded that of the alpha4 subunit, suggesting that a change in alpha4beta2 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.
- Published
- 2010