"Drug dependence is a complex behavior induced by psychostimulatory drugs, which affect the central brain reward circuitry by associating themselves with environmental cues. Long-term administration of the drugs results in the development of neural and behavioral plasticity, leading to addiction relapse even after long-term abstinence. Very little is known about the molecular and cellular adaptation that takes place during the processes.There is increasingly growing evidence indicating that small RNA pathways (microRNA and small interfering RNA) modulate drug-dependent behaviors however not much is known about the small RNAs and up or downstream targets of these pathways in these behaviors.C. elegans is a well established model for nicotine dependence and exhibits a variety of behavioral responses to nicotine, including acute response, adaptation, withdrawal and sensitization. In addition to that gene silencing pathways are also well studied in C. elegans thereby making it a perfect experimental model for this project.This project will focus on investigating the role of gene silencing pathways in nicotine dependence using C. elegans as model organism. The project will exploit the power of both forward/reverse genetic methods, and microarray technology along with mass spectrometry (MS) technique to eventually identify the genes that are up- or downregulated during nicotine dependence. Latest imaging techniques such as calcium-imaging for monitoring neuronal activity, and photo-activation or inhibition to stimulate or inhibit specific neurons, will be also utilized to better understand the function of the small RNA pathways at the subcellular level. The findings of this project will help in understanding the role of gene silencing pathways and its targets during nicotine dependence. In the long run the results could have a medical application, in developing therapeutics aimed to lessen withdrawal symptoms and thereby reducing drug dependence relapses."