Nicotine dependence involves complex interactions between multiple genes and environmental factors (Li 2008). There are a wide range of research approaches to understand the genetic influences on nicotine dependence, ranging from transgenic animal models to population studies. Pharmacological and molecular biology studies include in vitro receptor genetic mutations, as well as knock-out (KO) and point mutation knock-in animal models (Greenbaum and Lerer 2009). These studies evaluate the pharmacological and biochemical properties of specific gene manipulations to determine their contribution to nicotine dependence and/or nicotine withdrawal.