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.
Introduction and objectives: The ability to adapt to new task demands flexibly and to stabilise performance in the presence of distractors is termed cognitive control and is mediated by dopaminergic and cholinergic neurotransmission. We aimed to test the hypothesis that the effect of the cholinergic agonist nicotine on cognitive control depends on baseline dopamine levels. Methods: Thirty-eight healthy non-smokers (16 males; Mage=24.05 years) performed a cognitive control task including distractor and switch trials twice. Subjects were split into two parallel groups. One group received 2 g of L-tyrosine two hours prior to testing to manipulate dopamine availability experimentally, while the other group received placebo on both days. One hour later, both groups received in a within-subject design: on one day, a 7 mg nicotine patch; on the other day, a matched placebo. Response time costs for distractor and switch trials served as measures of cognitive stability and flexibility. Results: Nicotinic modulation reduced response time costs in switch trials and increased costs in distractor trials (nicotine×condition, p=0.027) with a trend-wise interaction between nicotine, L-tyrosine and trial type (nicotine×L-tyrosine×condition, p=0.068), which was due to stronger nicotine effects under L-tyrosine. Conclusions: Our data provide preliminary evidence that nicotine has opponent effects on cognitive stability and flexibility. Subjects who received the dopamine precursor L-tyrosine were more prone to nicotine effects on behaviours, which are improvements in cognitive flexibility at the cost of decreased cognitive stability.
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