A common pathway for the positive reinforcement associated with most, if not all, addictive drugs is the brain dopamine (DA) reward pathway (Koob 1992; Leshner and Koob 1999). Laboratory animal studies demonstrate that DA release in the ventral striatum (VST)/nucleus accumbens (NAc) underlies the reinforcing properties of nicotine (Koob 1992; Leshner and Koob 1999). Microdialysis (Damsma et al. 1989; Di Chiara and Imperato 1988; Pontieri et al. 1996; Sziraki et al. 2001) and lesion (Corrigall et al. 1992) studies in rats indicate that nicotine-induced DA release is strongest in this region, and is more robust than the DA release found in associated structures receiving dopaminergic input, such as the dorsal striatum (Di Chiara and Imperato 1988). These studies generally used nicotine dosages that simulated human cigarette smoking. Acute exposure to cigarette smoke and nicotine has been found to upregulate dopamine transporter mRNA in the ventral tegmental area (VTA) and substantia nigra (Li et al. 2004), and chronic exposure to cigarette smoke, more so than chronic nicotine alone, has also been found to upregulate D1 and D2 receptor mRNA in the
