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

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, α4β2 nAChRs were up-regulated in all brain regions, α6β2* nAChRs were down-regulated in the nucleus accumbens (NAc) and caudate-putamen, and α7 nAChRs were up-regulated in the caudal cerebral cortex (CCx); the up-regulation of α4β2α5 nAChRs in the CCx was also suggested. In the SA group, α4β2 up-regulation 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.