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A preliminary study suggests that nicotine and prefrontal dopamine affect cortico-striatal areas in smokers with performance feedback.

ABSTRACT: Nicotine and tonic dopamine (DA) levels [as inferred by catechol-O-methyl tranferase (COMT) Val158Met genotype] interact to affect prefrontal processing. Prefrontal cortical areas are involved in response to performance feedback, which is impaired in smokers. We investigated whether there is a nicotine?×?COMT genotype interaction in brain circuitry during performance feedback of a reward task. We scanned 23 healthy smokers (10 Val/Val homozygotes, 13 Met allele carriers) during two fMRI sessions while subjects were wearing a nicotine or placebo patch. A significant nicotine?×?COMT genotype interaction for BOLD signal during performance feedback in cortico-striatal areas was seen. Activation in these areas during the nicotine patch condition was greater in Val/Val homozygotes and reduced in Met allele carriers. During negative performance feedback, the change in activation in error detection areas such as anterior cingulate cortex (ACC)/superior frontal gyrus on nicotine compared to placebo was greater in Val/Val homozygotes compared to Met allele carriers. With transdermal nicotine administration, Val/Val homozygotes showed greater activation with performance feedback in the dorsal striatum, area associated with habitual responding. In response to negative feedback, Val/Val homozygotes had greater activation in error detection areas, including the ACC, suggesting increased sensitivity to loss with nicotine exposure. Although these results are preliminary due to small sample size, they suggest a possible neurobiological mechanism underlying the clinical observation that Val/Val homozygotes, presumably with elevated COMT activity compared to Met allele carriers and therefore reduced prefrontal DA levels, have poorer outcomes with nicotine replacement therapy.

SUBMITTER: Lee MR

PROVIDER: S-EPMC3890256 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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A preliminary study suggests that nicotine and prefrontal dopamine affect cortico-striatal areas in smokers with performance feedback.

Lee M R MR Gallen C L CL Ross T J TJ Kurup P P Salmeron B J BJ Hodgkinson C A CA Goldman D D Stein E A EA Enoch M A MA

Genes, brain, and behavior 20130411 5

Nicotine and tonic dopamine (DA) levels [as inferred by catechol-O-methyl tranferase (COMT) Val158Met genotype] interact to affect prefrontal processing. Prefrontal cortical areas are involved in response to performance feedback, which is impaired in smokers. We investigated whether there is a nicotine × COMT genotype interaction in brain circuitry during performance feedback of a reward task. We scanned 23 healthy smokers (10 Val/Val homozygotes, 13 Met allele carriers) during two fMRI sessions ...[more]

PMID: 23433232

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Project description:Abstract Nicotine exposure is associated with regional changes in brain nicotinic acetylcholine receptors subtype expression patterns as a function of dose and age at the time of exposure. Moreover, nicotine dependence is associated with changes in brain circuit functional connectivity, but the relationship between such connectivity and concomitant regional distribution changes in nicotinic acetylcholine receptor subtypes following nicotine exposure is not understood. Although smoking typically begins in adolescence, developmental changes in brain circuits and nicotinic acetylcholine receptors following chronic nicotine exposure remain minimally investigated. Here, we combined in vitro nicotinic acetylcholine receptor autoradiography with resting state functional magnetic resonance imaging to measure changes in [3H]nicotine binding and α4ß2 subtype nicotinic acetylcholine receptor binding and circuit connectivity across the brain in adolescent (postnatal Day 33) and adult (postnatal Day 68) rats exposed to 6 weeks of nicotine administration (0, 1.2 and 4.8 mg/kg/day). Chronic nicotine exposure increased nicotinic acetylcholine receptor levels and induced discrete, developmental stage changes in regional nicotinic acetylcholine receptor subtype distribution. These effects were most pronounced in striatal, thalamic and cortical regions when nicotine was administered during adolescence but not in adults. Using these regional receptor changes as seeds, resting state functional magnetic resonance imaging identified dysregulations in cortico-striatal-thalamic-cortical circuits that were also dysregulated following adolescent nicotine exposure. Thus, nicotine-induced increases in cortical, striatal and thalamic nicotinic acetylcholine receptors during adolescence modifies processing and brain circuits within cortico-striatal-thalamic-cortical loops, which are known to be crucial for multisensory integration, action selection and motor output, and may alter the developmental trajectory of the adolescent brain. This unique multimodal study significantly advances our understanding of nicotine dependence and its effects on the adolescent brain. Keeley et al. present a multimodal study assessing changes in nicotinic receptor subtype expression and resting-state functional connectivity in adolescents and adults after chronic nicotine administration. Following exposure, differences in receptor density and resting-state functional connectivity were found in adolescents but not adults, particularly in the cortical, striatal and thalamic regions. Graphical Abstract Graphical abstract

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A preliminary study suggests that nicotine and prefrontal dopamine affect cortico-striatal areas in smokers with performance feedback.

Publications

A preliminary study suggests that nicotine and prefrontal dopamine affect cortico-striatal areas in smokers with performance feedback.

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