br Material and methods br Results br Discussion This study

Material and methods
Results
Discussion This study took a first step at evaluating the comparative neural responses during incentive anticipation among adolescents across the three most prevalent substances of abuse (alcohol, tobacco, and cannabis). We focused on the NAcc, an area within the VS that has been strongly implicated in reward processing in both the developmental and addiction literatures (e.g., Knutson et al., 2001a; Ernst et al., 2005; Heitzeg et al., 2014). In this preliminary examination, we observed whole GSK-J1 sodium salt Supplier effects supporting the validity of the MID task among 14–18 year olds. Our ROI analysis indicated significant differences in NAcc activation during reward anticipation by substance use group, with a unique response pattern emerging among the tobacco-only group. Of note, we observed nearly identical patterns of reward responding in the left and right NAcc, which strengthens our confidence in these results. We hypothesized decreased reward responding for youth in the tobacco-only group compared to the alcohol-only, cannabis-only, cannabis+tobacco and control groups (Nestor et al., 2010; Peters et al., 2011). Given the lack of published research on polysubstance users of alcohol, tobacco and cannabis, we did not have clear directional hypotheses about this group, and thus treated this portion of the analysis as exploratory. Contrary to our a priori hypotheses, no differences emerged between the tobacco-only and cannabis-only groups. However, as predicted, we observed differences in reward responding in bilateral NAcc in the tobacco-only group compared to the non-using control group. Specifically, we found decreased activation in the tobacco-only compared to the control group, which is consistent with previous findings suggesting that tobacco is associated with blunted responses to non-substance-based rewards (such as financial incentives) in the VS (e.g., Peters et al., 2011; Rose et al., 2013; Wilson et al., 2014). We also observed greater responses in the alcohol-only compared to the tobacco-only group for the highest level of reward, which is consistent with some prior research showing increased reward responding in adolescent drinkers (e.g., Heitzeg et al., 2014). Given parallels with the animal literature in this area, Leading strand is possible that acute withdrawal from nicotine may explain the reduced striatal activation by reward cues observed among adolescent smokers in this study (Epping-Jordan et al., 1998). Using animal models, nicotine withdrawal has been linked to reduced dopamine release in the NAcc (Hildebrand et al., 1998), blunting both tonic and phasic dopaminergic activity in the striatum (Zhang et al., 2012). Evidence suggests that upregulated dopamine transporter activity contributes to the decrease in extracellular striatal dopamine observed during early nicotine withdrawal (Hadjiconstantinou et al., 2011). As subjects in this study were required to abstain from smoking cigarettes for 3hours before the scanning session, it is possible that the experience of acute nicotine withdrawal may have influenced NAcc activation during the scan. Future studies may consequently consider measuring withdrawal symptoms before the MID task. Note that the tobacco-only group also showed decreased reward responding compared to the polysubstance groups (cannabis+tobacco; cannabis+tobacco+alcohol), who may have also been experiencing nicotine withdrawal. Importantly, this finding was expected based on prior work demonstrating that tobacco+cannabis users have greater striatal reward responses than tobacco-only users (van Hell et al., 2010; Nestor et al., 2010). Yet, comparison with existing studies, including the Nestor study (Nestor et al., 2010), should be done with caution, as subjects in the present study reported heavier smoking; thus, the case could be made that this set of adolescents might have a greater propensity to experience acute nicotine withdrawal. Notably, our results cannot be attributed to greater tobacco use in the tobacco-only versus polysubstance groups, as the design of the study purposefully ensured that all three groups were matched for equal levels of tobacco use. Additionally, as we found no evidence of differences in impulsivity across our groups, it is unlikely that our activation findings may have been driven by personality traits associated with increased reward responsiveness.