Aim: 

Experimental studies of the effects of chronic exposure to nicotine (or nicotinic drugs) on neuronal nicotinic receptor (nAChR) subtypes may help to clarify the tolerance, dependence and withdrawal syndrome associated with nicotine addiction. Furthermore, given the substantial decrease in the number of nAChRs during aging, Alzheimer's and Parkinson's diseases, and the findings of epidemiology and in vitro studies suggesting that nicotine may protect against Parkinson's disease, investigating the consequences of the protracted use of nicotinic drugs might improve our understanding of the pathophysiological mechanisms of certain neurodegenerative conditions.

Methods: 

We studied the effect of chronic nicotine treatment on the expression of nicotinic receptors in in vitro studies of primary neurons and neuroblastoma cells, and in vivo studies of rats chronically administered with nicotine by means of an Alzet minipump

We used various biochemical and pharmacological approaches to analyse the presence of various subtypes and their regulation by nicotine

Results: 

The immunoprecipitation and immunopurification studies showed that chronic nicotine treatment increased the number high affinity receptors present on the cell surface and inside neurons. This increase was due to the enhanced expression of b2*?*??containing subtypes, and not to changes in subunit mRNA translation or receptor half-life.

Furthermore, it did not depend on the agonist/antagonist properties of the drugs, and did not involved other receptor classes.

The same analysis of rat tissues demonstrated that nicotine selectively up-regulates the a4b2 subtypes in some but not all brain areas, and downregulates the expression of a6b2-containing receptors in the mesostriatal dopaminergic areas.

Conclusions: 

The in vitro results indicate that chronic treatment increases the number of nAChRs containing b2 ?and a7? subunits on the plasma membrane, of neurons where they were functionally active.

The in vivo results indicate that there is only an increase in b2*-containing receptors and that this increase is region and subtype specific.