A recent PET study examined associations of dopaminergic gene variants with smoking-induced DA release using the radio-tracer [11C]raclopride and observed that smokers carrying variants associated with reduced dopamin-ergic tone (i.e., SLC6A3 9-repeat allele, DRD4 S allele, or the COMT Val/Val genotypes) had greater smoking-induced decreases in raclopride binding in the striatum, indicative of greater DA release in this region (Brody et al, 2006). A perfusion-MRI study after overnight abstinence found that genetic variants associated with reduced dopaminergic tone (DRD2-141
DelC variant and COMT Val/Val genotype) and increased endogenous opioid binding (OPRM1 AA genotype) had greater regional abstinence-induced rCBF increases that may increase risk for relapse (Wang et al, 2008b). Jacobsen and colleagues (2006) investigated the association between the DRD2 C957T polymorphism and brain activation during a working memory task called the N-back task following pretreatment with either nicotine or placebo patch. The N-back task requires responses based on certain rules if the current stimulus is identical to the stimuli that have appeared previously. For example in the 1-back condition the participant is required to respond if the stimulus on the screen is identical to the one that appeared right before the current one. The task is progressively more difficult as the participant has to keep in their working memory stimuli that have appeared 2 (2-back) or 3 (3-back) times before the current one, increasing their working memory load (Loughead et al, 2009). Carriers of the 957T allele had greater activation during the most challenging condition of the task in the left anterior insula, left cerebellum, right and middle occipital gyri, right fusiform, and the right middle temporal gyrus while they were on the nicotine patch. Conversely, individuals with the DRD2 957 C/C genotype showed decreased activation in these areas on the nicotine patch. This difference by genotype could be due to imbalances in levels of dopamine among participants with the */T allele after nicotine patch administration (Jacobsen et al, 2006). A subsequent study examined the effects of COMT genotype on abstinence-induced cognitive deficits using a visual N-back task (Loughead et al, 2009). During abstinence the Val/Val homozygotes had lower activation in the bilateral dorsolateral pre-frontal cortices and medial prefrontal cortex while they performed the toughest condition of the task, compared to the other genotype groups. The Val/Val homozygotes also had slower reaction times during this condition of the N-back task (Loughead et al, 2009). Abstinence-induced cognitive deficits in the Val/Val group may contribute to the greater relapse risk observed in this group (Colilla et al, 2005). McClernon and colleagues (2007) observed an association between the DRD4 VNTR and smoking cue-reactivity; individuals with the longer-repeat alleles had greater BOLD (blood oxygen-level dependent) activation to the smoking cues in the right superior frontal gyrus and the right insula (McClernon et al, 2007).
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