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, 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.
Moretti
Milena
M
Consiglio Nazionale delle Ricerche, Neuroscience Institute-Milano, Cellular and Molecular Pharmacology, Department of Medical Pharmacology, University of Milan, Milan, Italy.
Mugnaini
Manolo
M
Tessari
Michela
M
Zoli
Michele
M
Gaimarri
Annalisa
A
Manfredi
Irene
I
Pistillo
Francesco
F
Clementi
Francesco
F
Gotti
Cecilia
C
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D047468:Immunoprecipitation; D007262:Infusions, Intravenous; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D012646:Self Administration
D011978:Receptors, Nicotinic; D009538:Nicotine