Rodent models of nicotine withdrawal syndrome.

Simple, rapid and inexpensive rodent models of nicotine physical dependence and withdrawal syndrome have proved useful for preliminary screening of smoking cessation treatments. They have led to an exponential increase of knowledge regarding the underlying neurobiological mechanisms of dependence and withdrawal syndrome. The human nicotine withdrawal syndrome in smoking cessation is variable and multidimensional, involving irritability, anxiety, depression, cognitive and attentional impairments, weight gain, sleep disturbances, and craving for nicotine. Aside from sleep disturbances, analogous phenomena have been seen in rodent models using different measures of withdrawal intensity. It appears likely that different withdrawal phenomena may involve some partially divergent mechanisms. For example, depression-like phenomena may involve alterations in mechanisms such as the mesolimbic dopamine pathway from the ventral tegmental area to the nucleus accumbens. Irritability and anxiety may involve alterations in endogenous opioid systems and other regions, such as the amygdala. This chapter reviews many additional anatomical, neurochemical, and developmental elements that impact nicotine physical dependence.