Effects of Nicotine Deprivation and Replacement on BOLD-fMRI Response to Smoking Cues as a Function of DRD4 VNTR Genotype

Xu, Xiaomeng; Clark, Uraina S.; David, Sean P.; Mulligan, Richard C.; Knopik, Valerie S.; McGeary, John E.; MacKillop, James; McCaffery, Jeanne M.; Niaura, Raymond; Sweet, Lawrence H.

doi:10.1093/ntr/ntu010

Cited by 11 publications

(8 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acute NRT administration following overnight abstinence was associated with greater smoking cue‐elicited striatal and amygdalar activation in a sample of non‐treatment‐seeking smokers (Xu et al . ); yet, discrepancies in treatment‐seeking status and duration of abstinence complicate the integration of these NRT results with those previously described.…”

Section: Pharmacological Treatment Effects On Neural Substrates Of Cumentioning

confidence: 78%

Neural substrates of cue reactivity: association with treatment outcomes and relapse

et al. 2015

View full text Add to dashboard Cite

Given the strong evidence for neurological alterations at the basis of drug dependence, functional magnetic resonance imaging (fMRI) represents an important tool in the clinical neuroscience of addiction. fMRI cue-reactivity paradigms represent an ideal platform to probe the involvement of neurobiological pathways subserving the reward/motivation system in addiction and potentially offer a translational mechanism by which interventions and behavioral predictions can be tested. Thus, this review summarizes the research that has applied fMRI cue-reactivity paradigms to the study of adult substance use disorder treatment responses. Studies utilizing fMRI cue-reactivity paradigms for the prediction of relapse, and as a means to investigate psychosocial and pharmacological treatment effects on cue-elicited brain activation are presented within four primary categories of substances: alcohol, nicotine, cocaine, and opioids. Lastly, suggestions for how to leverage fMRI technology to advance addiction science and treatment development are provided.

show abstract

Section: Pharmacological Treatment Effects On Neural Substrates Of Cumentioning

confidence: 78%

Neural substrates of cue reactivity: association with treatment outcomes and relapse

et al. 2015

View full text Add to dashboard Cite

show abstract

“…For example, Bruijnzeel et al (2014) observed greater brain activation to nicotine administration (compared to saline injection) in rats in brain areas commonly associated with reward processing (e.g., nucleus accumbens, amygdala, and insula) and behavioral planning/imagining (e.g., motor and somatosensory cortices). In abstinent cigarette smokers, Xu et al (2014) reported that wearing a nicotine patch resulted in greater brain activation to cigarette videos in the bilateral ventral striatum and left amygdala when compared with neutral videos. Notably, the placebo patch did not have such an effect, suggesting that nicotine administration was responsible for these cue-related neural responses.…”

Section: Discussionmentioning

confidence: 99%

“…Phenomenologically, this may be related to increased expectations of use, particularly if they were not fully sated by the drug administration (e.g., see Xu et al, 2014). To explore this option more fully in our participants, we conducted post-hoc analyses to assess the degree of fulfilment our participants felt from the vaping protocol.…”

Section: Discussionmentioning

confidence: 99%

Cue-reactivity in experienced electronic cigarette users: Novel stimulus videos and a pilot fMRI study

Nichols

Foulds

Yingst

et al. 2016

Brain Research Bulletin

View full text Add to dashboard Cite

Some individuals who try electronic cigarettes (e-cigarettes) continue to use long-term. Previous research has investigated the safety of e-cigarettes and their potential for use in smoking cessation, but comparatively little research has explored chronic or habitual e-cigarette use. In particular, the relationship between e-cigarette cues and craving is unknown. We sought to bridge this gap by developing a novel set of e-cigarette (salient) and electronic toothbrush (neutral) videos for use in cue-reactivity paradigms. Additionally, we demonstrate the utility of this approach in a pilot fMRI study of 7 experienced e-cigarette users. Participants were scanned while viewing the cue videos before and after 10 minute use of their own e-cigarettes (producing an 11.7 ng/ml increase in plasma nicotine concentration). A significant session (pre- and post-use) by video type (salient and neutral) interaction was exhibited in many sensorimotor areas commonly activated in other cue-reactivity paradigms. We did not detect significant cue-related activity in other brain regions notable in the craving literature. Possible reasons for this discrepancy are discussed, including the importance of matching cue stimuli to participants’ experiences.

show abstract

“…Individuals who carry at least one “long” allele ( DRD4-L ) are less common in the general population. Analysis of cell lines indicate that DRD4-L is associated with reduced ligand binding and reduced cyclic adenosine monophosphate formation when dopamine is receptor-bound (Asghari et al, 1995), suggesting reduced dopaminergic tone in the mesocorticolimbic pathway (Brody et al, 2006; Rivera et al, 2002; Xu et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

“…The presence of the DRD4-L allele in smokers has also been associated with enhanced reactivity to smoking cues (Hutchison et al, 2002; Munafo and Johnstone, 2008). Furthermore, DRD4-L smokers show greater activation of right superior frontal gyrus and right insula in response to smoking cues (McClernon et al, 2007), as well as differences in amygdala activation (Xu et al, 2014) using functional magnetic resonance imaging (fMRI).…”

Section: Introductionmentioning

confidence: 99%

Dopaminergic genetic variation moderates the effect of nicotine on cigarette reward

et al. 2015

View full text Add to dashboard Cite

Rationale Cigarette smoking is influenced by nicotine’s effects on dopaminergic activity in the mesocorticolimbic pathway. This activity appears to be moderated by genetic variation, specifically a variable number tandem repeat (VNTR) polymorphism in the third exon of the dopamine receptor gene (DRD4). Objective We examined whether this polymorphism along with three DRD4 Single Nucleotide Polymorphisms (SNPs: rs936460, rs936461, and rs12280580) moderate the influence of nicotine on subjective responses to cigarettes. Methods White, non-Hispanic smokers (n=96, cigarettes/day ≥ 15) attended two double-blind, counterbalanced experimental sessions, each preceded by overnight smoking abstinence. Participants smoked four nicotine (8.9 mg) or placebo (1.0 mg) cigarettes per session, with each cigarette followed by completion of the modified Cigarette Evaluation Questionnaire (mCEQ). Results We examined the mCEQ composite score via 2×2×4 ANOVAs with genotype (major homozygotes versus minor carriers) as the between-subject factor and nicotine content and smoking bout as within-subject factors. Although DRD4 VNTR variation did not moderate overall nicotine response, there was a moderation of nicotine response over successive cigarettes. Smokers with fewer than 7 repeats for the DRD4 VNTR reported markedly reduced craving, increased satisfaction, and a greater calming effect in response to earlier smoked nicotine cigarettes, whereas those with 7 or more repeats did not. In addition, minor carriers for all 3 DRD4 SNPs displayed blunted overall response to nicotine. Conclusion These findings provide support for DRD4 variation as an informative predictor of subjective responses to nicotine. We discuss how these data may lead to improved tailoring of smoking cessation pharmacotherapies.

show abstract

Effects of Nicotine Deprivation and Replacement on BOLD-fMRI Response to Smoking Cues as a Function of DRD4 VNTR Genotype

Abstract: introduction: Reactivity to smoking cues is an important factor in the motivation to smoke and has been associated with the dopamine receptor 4 variable number tandem repeat (DRD4 exon III VNTR) polymorphism. However, little is known about the associated neural mechanisms.

Cited by 11 publications

References 57 publications

Neural substrates of cue reactivity: association with treatment outcomes and relapse

Neural substrates of cue reactivity: association with treatment outcomes and relapse

Cue-reactivity in experienced electronic cigarette users: Novel stimulus videos and a pilot fMRI study

Dopaminergic genetic variation moderates the effect of nicotine on cigarette reward

Contact Info

Product

Resources

About