This is an important possibility that deserves further investigation. It should be noted selleck kinase inhibitor that nicotine patch treatment significantly reduced negative affective symptoms during smoking cessation in this study (Gilbert et al., 2009), indicating that other factors could have attenuated the craving-suppressing effects of NRT. Craving has been thought to be one key motivational factor for former smokers to lapse/relapse after abstinence (Drummond, 2001; Killen & Fotmann, 1997; Shiffman et al., 1997). In relation to recent evidence for female A1 carriers being less likely to be abstinent after NRT (Munaf��, Johnstone, et al., 2009), our observation that A1 carriers experienced stronger craving for smoking not only during initial days of abstinence but also persistently during the last 2-week+ phase of the 6-week study period suggests that the link between the A1 genotype and poorer smoking cessation outcome may be, at least partially, mediated by craving.

However, more work is needed to answer this question, as the overall evidence supporting the association of the TaqIA polymorphism and smoking behavior including treatment outcome remains equivocal (for a review, see Munaf��, Timpson, et al., 2009). From yet another perspective, unlike broad measures of smoking behavior such as smoking status, smoking rate, and abstinence rate, which presumably are determined by multiple factors including multiple genes, craving can be viewed as a more specific phenotype that is closely related to the TaqIA polymorphism.

The current finding highlights the possibility that this genetic variant Entinostat may be mostly associated with treatment outcome in cases where craving is a crucial trigger for relapse. Effects on smoking for pleasure Despite the well-established role of the mesolimbic DA system in acute positive reinforcing effects of nicotine as well as other drugs, we found significant differences in smoking for pleasure-seeking between only A1 carriers and A2/A2 female smokers, with the former group reporting a higher probability of smoking for this purpose. If validated in future studies, the lack of effects of the TaqIA variant on smoking for pleasure in men may provide some support for the incentive sensitization (IS) theory of drug craving (Berridge, 2007; Robinson & Berridge, 1993). Evidence favoring IS theory suggests that DA is neither necessary nor sufficient to mediate hedonic liking for sensory pleasures. Instead, the DA system is thought to contribute causally to IS, a process in which stimuli or cues associated with drug use are attributed incentive salience, that is, rewarding properties that make these stimuli attractive and wanted.