Modulation of nicotine effects on selective attention by DRD2 and CHRNA4 gene polymorphisms

Ahrens, Stefan; Markett, Sebastian; Breckel, Thomas P. K.; Behler, Oliver; Reuter, Martin; Thiel, Christiane M.

doi:10.1007/s00213-015-3869-2

Cited by 16 publications

(12 citation statements)

References 45 publications

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“…The cardiovascular effects of nicotine are in line with many prior findings with an increase in heart rate and/or blood pressure under nicotine [10,20,46,47]. …”

Section: Discussionsupporting

confidence: 71%

EEG Source Reconstruction in Male Nonsmokers after Nicotine Administration during the Resting State

Ranzi

Thiel²,

Herrmann³

2016

Neuropsychobiology

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Modern psychopharmacological research in humans focuses on how specific psychoactive molecules modulate oscillatory brain activity. We present state-of-the-art EEG methods applied in a resting-state drug study. Thirty healthy male nonsmokers were randomly allocated either to a nicotine group (14 subjects, 7 mg transdermal nicotine) or a placebo group (16 subjects). EEG activity was recorded in eyes-open (EO) and eyes-closed (EC) conditions before and after drug administration. A source reconstruction (minimum norm algorithm) analysis was conducted within a frequency range of 8.5-18.4 Hz subdivided into three different frequency bands. During EO, nicotine reduced the power of oscillatory activity in the 12.5- to 18.4-Hz frequency band in the left middle frontal gyrus. In contrast, in the EC condition, nicotine reduced the power in the 8.5- to 10.4-Hz frequency band in the superior frontal gyri and in the 10.5- to 12.4-Hz and 12.5- to 18.4-Hz frequency bands in the supplementary motor areas. In summary, nicotine reduced the power of the 12.5- to 18.4-Hz band in the left middle frontal gyrus during EO, and it reduced power from 8.5 to 18.4 Hz in a brain area spanning from the superior frontal gyri to the supplementary motor areas during EC. In conclusion, the results suggest that nicotine counteracts the phenomenon of anteriorization of α activity, hence potentially increasing the level of vigilance.

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“…The cardiovascular effects of nicotine are in line with many prior findings with an increase in heart rate and/or blood pressure under nicotine [10,20,46,47]. …”

Section: Discussionsupporting

confidence: 71%

EEG Source Reconstruction in Male Nonsmokers after Nicotine Administration during the Resting State

Ranzi

Thiel²,

Herrmann³

2016

Neuropsychobiology

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“…The genetic polymorphisms investigated here may impact such dynamic interplay and modulate the effects of systemically administered nicotine. We have recently shown that DRD2 T-/CHRNA4 C+ subjects are also more responsive to the effects of nicotine on distractor interference, which corroborates the present findings [47]. A recent study further underlines the interactions between cholinergic and dopaminergic polymorphisms in showing epistatic effects of CHRNA5 and DRD2 on working memory and prefrontal cortex activity [48].…”

Section: Discussionsupporting

confidence: 89%

“…A recent study further underlines the interactions between cholinergic and dopaminergic polymorphisms in showing epistatic effects of CHRNA5 and DRD2 on working memory and prefrontal cortex activity [48]. Taken together, it can be concluded that the attentional effects of nicotine reported here and in our prior study [47] are primarily seen in subjects with high dopaminergic activity (i.e. DRD2 T-) and a presumably higher rate of nicotinic receptors in high affinity state (i.e.…”

Section: Discussionsupporting

confidence: 77%

“…Prior behavioural evidence indicates that CHRNA4 C allele carriers are stronger influenced by distractors and that systemic administration of nicotine reduces distractor processing [9, 52]. As mentioned above we have recently extended these findings by providing evidence that the effects of nicotine on distractor interference depend on an interaction of the DRD2 and CHRNA4 polymorphism [47]. Even though the paradigm here did not involve distractors, we were able to show that the pulvinar is one of the brain regions where interindividual variability in response to nicotine can be used to decode CRHNA4/DRD2 genotype.…”

Section: Discussionsupporting

confidence: 53%

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Nicotinergic Modulation of Attention-Related Neural Activity Differentiates Polymorphisms of DRD2 and CHRNA4 Receptor Genes

et al. 2015

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Cognitive and neuronal effects of nicotine show high interindividual variability. Recent findings indicate that genetic variations that affect the cholinergic and dopaminergic neurotransmitter system impact performance in cognitive tasks and effects of nicotine. The current pharmacogenetic functional magnetic resonance imaging (fMRI) study aimed to investigate epistasis effects of CHRNA4/DRD2 variations on behavioural and neural correlates of visuospatial attention after nicotine challenge using a data driven partial least squares discriminant analysis (PLS-DA) approach. Fifty young healthy non-smokers were genotyped for CHRNA4 (rs1044396) and DRD2 (rs6277). They received either 7 mg transdermal nicotine or a matched placebo in a double blind within subject design prior to performing a cued target detection task with valid and invalid trials. On behavioural level, the strongest benefits of nicotine in invalid trials were observed in participants carrying both, the DRD2 T- and CHRNA4 C+ variant. Neurally, we were able to demonstrate that different DRD2/CHRNA4 groups can be decoded from the pattern of brain activity in invalid trials under nicotine. Neural substrates of interindividual variability were found in a network of attention-related brain regions comprising the pulvinar, the striatum, the middle and superior frontal gyri, the insula, the left precuneus, and the right middle temporal gyrus. Our findings suggest that polymorphisms in the CHRNA4 and DRD2 genes are a relevant source of individual variability in pharmacological studies with nicotine.

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“…, gene envolvido na modulação da locomoção, reforço, memória e aprendizagem e têm sido associado à diversas patologias psiquiátricas na literatura como, por exemplo, esquizofrenia (Lencz et al, 2015;Yao et al, 2015), depressão (Savitz et al, 2013;Pearson-Fuhrhop et al, 2014); jogo patológico (Hillemacher et al, 2015) e dependência de álcool (Delis et al, 2015), nicotina (Ahrens et al, 2015;Ma et al, 2015), opiáceos (Nelson et al, 2014;Levran et al, 2015), maconha (Colizzi et al, 2015;DiNieri et al, 2015) e cocaína (Noble et al, 1993). A relação entre o gene DRD2 e o abuso/dependência de cocaína têm sido investigada em diversos estudos em animais (Lee et al, 2006;Bertran-Gonzalez et al, 2008;Lawhorn et al, 2013) e humanos.…”

Section: Drd2 (Dopamine Receptor D2)unclassified

Estudos epigenéticos em dependentes de crack e cocaína: investigação da metilação global do genoma

Camilo¹

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AGRADECIMENTOSAgradeço primeiramente a Deus pela saúde, fé, perseverança e por iluminar o meu caminho durante esta caminhada.Aos meus pais, Ana Maria e Izilmar, por sua história de sucesso na educação dos filhos diante todas as adversidades. Agradeço pela educação que me deram, pela confiança, pelas broncas e por tudo que fizeram por mim com o objetivo de me formar pessoalmente e profissionalmente.Ao meu irmão, Ronaldo, meu melhor amigo, por seus conselhos, ensinamentos e por acreditar em mim e no meu potencial em todos os momentos. Aos meus familiares, por me incentivar nas horas mais difíceis e nas decisões tomadas, por compartilhar e sempre estar ao meu lado ao longo das minhas conquistas.Aos amigos, aos que se foram e aos que permanecem em minha vida até hoje, por todas as palavras de incentivo e persistência.Ao orientador Professor Doutor Homero Vallada, pelo voto de confiança em me acolher como orientanda. Por sua paciência, experiência e ensinamentos nessa jornada. E, principalmente, por incentivar minha maturidade acadêmica e pessoal. À Banca de qualificação, composta pela Profa. Márcia Scazufca, Prof.Guilherme Messas e Prof. Hermano Tavares, pelas sugestões e orientações adequadas ao aprimoramento dessa pesquisa.

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Modulation of nicotine effects on selective attention by DRD2 and CHRNA4 gene polymorphisms

Abstract: The effects of nicotine on distractor interference are modulated synergistically by cholinergic and dopaminergic genetic variations. Hence, both genes may contribute to the often reported individual variability in cognitive and neural effects of nicotine.

Cited by 16 publications

References 45 publications

EEG Source Reconstruction in Male Nonsmokers after Nicotine Administration during the Resting State

EEG Source Reconstruction in Male Nonsmokers after Nicotine Administration during the Resting State

Nicotinergic Modulation of Attention-Related Neural Activity Differentiates Polymorphisms of DRD2 and CHRNA4 Receptor Genes

Estudos epigenéticos em dependentes de crack e cocaína: investigação da metilação global do genoma

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