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Acute, chronic nicotine dependence should be targeted differently

Recent findings indicated a double disassociation between chronic and acute effects of nicotine dependence on reward sensitivity and cognitive flexibility within overlapping mesocorticolimbic regions.

“Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment,” Elise Lesage, PhD, of the National Institute on Drug Abuse, and colleagues wrote.

To assess effects of nicotine dependence and stimulation of nicotinic acetylcholine on reward sensitivity and cognitive flexibility, researchers conducted a randomized, double-blind, placebo-controlled trial of 24 nicotine-dependent smokers and 20 nonsmokers. Study participants completed probabilistic reversal learning task while undergoing functional MRI. Smokers abstained from cigarette smoking for 12 hours for all sessions. Study participants underwent MRI twice while receiving varenicline and twice while receiving placebo, wearing a nicotine or placebo patch. Mean age ranged from 35.8 years to 30.4 years.

Computational modeling analysis suggested that abstinent smokers exhibited increased impulsivity during withdrawal, which was mitigated with nicotine and varenicline.

Decreased mesocorticolimbic activity associated with cognitive flexibility among abstinent smokers was restored to levels comparable to nonsmokers after stimulation of nicotinic acetylcholine receptors.

Neural markers of decreased reward sensitivity in the dorsal striatum and anterior cingulate cortex were not alleviated by nicotine or varenicline among smokers.

“This study highlights the need to dissociate acute drug associated effects from effects associated with chronic drug dependence, and to consider both mental computations and their anatomical substrate,” the researchers wrote. “Finally, the results provide a neural basis for the efficacy of nicotine replacement therapy and varenicline as smoking cessation tools, particularly associated with cognitive flexibility.” – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.