If smokers carrying the l/l allele experience greater activation of appetitive (approach/reward) pathways during smoking than their s/s or s/l counterparts, this could indicate that nicotine plays a significant role in the activation of appetitive structures among l/l smokers. Research has found that the long (l) variant of the 5-HTTLPR may be associated with increased transcription of the serotonin transporter, increased reuptake of serotonin from the synaptic cleft, and overall lower levels of serotonin in the synapse (Murphy et al., 2001), though not all research supports this (Javors et al., 2005; Johnson et al., 2008; Shioe et al., 2003; Willeit et al., 2000). One implication of these findings is that l/l smokers may use nicotine to enhance serotonin levels compared to non-l allele smokers. Moreover, this may also suggest that l/l carriers are more likely to become dependent smokers, a contention which is supported by three studies (Ishikawa et al., 1999; Kremer et al., 2005). An additional implication is that l/l smokers might also be more likely to relapse after quitting smoking compared to non-l smokers.
