Objective
Tobacco smoking is one of the major preventable causes of morbidity and mortality , as it increases the incidence of lung cancer, pulmonary , respiratory and cardiovascular diseases. Smoking is mainly due to the addictive properties of nicotine, which stimulates neuronal cholinergic-nicotinic receptors (nAChRs ), but insufficient knowledge of the mechanisms underlying this dependence has so far prevented rational anti-smoking interventions. The aim of this project is to extend our knowledge of the mechanisms leading and maintaining tobacco smoking To this end, we will study:
a) the nAChR subtypes involved in nicotine addiction in animal models and humans, their functional and pharmacological properties, their sub cellular localization and how nicotine changes their expression and activation using classical neurochemical, molecular and cellular techniques.
b ) the long-term effects of nicotine on gene expression, using DNA micro arrays in human cell lines because chronic exposure to addictive drugs leads to long-term changes in gene expression in certain brain structures that may be pathophysiologically relevant in maintaining addiction.
c ) how nicotine increases the release of dopamine (DA) in dopaminergic neurons and whether DA plays a role in the acquisition of nicotine dependence.
d) the correlations between the molecular and cellular results and behavior by using new rodent models of nicotine addiction to perform behavioral experiments in wild and single or combined alpha7, alpha4, beta2 KO animals;
e ) the possible role of genetic determinants in human nicotine addiction by seeking polymorphisms in the promoters of nicotinic subunits in a selected population of smokers and non-smokers.
Fields of science
Topic(s)
Data not availableCall for proposal
Data not availableFunding Scheme
NET - Research network contractsCoordinator
20129 MILANO
Italy