Neural Basis of Smoking-Induced Relief of Craving and Negative Affect: Contribution of Nicotine

TY - JOUR

T1 - Neural Basis of Smoking-Induced Relief of Craving and Negative Affect: Contribution of Nicotine

AU - Faulkner, Paul

AU - Ghahremani, Dara G

AU - Tyndale, Rachel F

AU - Paterson, Neil

AU - Cox, Chelsea M

AU - Ginder, Nathaniel

AU - Hellemann, Gerhard S

AU - London, Edythe D

PY - 2019/8/13

Y1 - 2019/8/13

N2 - Smoking-induced relief of craving and withdrawal promotes continuedcigarette use. Understanding how relief is produced, and the role ofnicotine in this process, may facilitate development of new smokingcessationtherapies. As the US Food and Drug Administration considerssetting a standard for reduced nicotine content in cigarettes to improvepublic health, knowledge of how nicotine contributes to relief also caninform policy. We assessed effects of nicotine using resting state functionalMRI and behavioral assessments of craving and negative affect. Twentyoneyoung (18-25 years old) daily smokers underwent overnightabstinence on 4 days. On each of the following mornings, they self-ratedtheir cigarette craving and negative affect, and underwent resting-statefMRI before and after smoking a cigarette that delivered 0.027, 0.110,0.231, or 0.763 mg nicotine. Functional connectivity between the anteriorinsula and anterior cingulate cortex (ACC), and between the nucleusaccumbens and orbitofrontal cortex (OFC), was assessed. Smoking reducedcraving, negative affect and nucleus accumbens-OFC connectivityirrespective of nicotine dose, with positive correlations of the effects onbehavioral and connectivity measures. Only the highest nicotine dose(0.763 mg) reduced right anterior insula-ACC connectivity; this reductionwas positively correlated with the behavioral effects of the 0.763-mg doseonly. While nicotine-based therapies may act on right anterior insula-ACCfunctional circuits to facilitate smoking cessation, non-nicotine (e.g., theconditioned, sensorimotor) aspects of smoking may promote cessation byreducing OFC-accumbens connectivity to alleviate withdrawal.© 2018, Society for the Study of Addiction. The attached document (embargoed until 11/10/2019) is an author produced version of a paper published in ADDICTION BIOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

AB - Smoking-induced relief of craving and withdrawal promotes continuedcigarette use. Understanding how relief is produced, and the role ofnicotine in this process, may facilitate development of new smokingcessationtherapies. As the US Food and Drug Administration considerssetting a standard for reduced nicotine content in cigarettes to improvepublic health, knowledge of how nicotine contributes to relief also caninform policy. We assessed effects of nicotine using resting state functionalMRI and behavioral assessments of craving and negative affect. Twentyoneyoung (18-25 years old) daily smokers underwent overnightabstinence on 4 days. On each of the following mornings, they self-ratedtheir cigarette craving and negative affect, and underwent resting-statefMRI before and after smoking a cigarette that delivered 0.027, 0.110,0.231, or 0.763 mg nicotine. Functional connectivity between the anteriorinsula and anterior cingulate cortex (ACC), and between the nucleusaccumbens and orbitofrontal cortex (OFC), was assessed. Smoking reducedcraving, negative affect and nucleus accumbens-OFC connectivityirrespective of nicotine dose, with positive correlations of the effects onbehavioral and connectivity measures. Only the highest nicotine dose(0.763 mg) reduced right anterior insula-ACC connectivity; this reductionwas positively correlated with the behavioral effects of the 0.763-mg doseonly. While nicotine-based therapies may act on right anterior insula-ACCfunctional circuits to facilitate smoking cessation, non-nicotine (e.g., theconditioned, sensorimotor) aspects of smoking may promote cessation byreducing OFC-accumbens connectivity to alleviate withdrawal.© 2018, Society for the Study of Addiction. The attached document (embargoed until 11/10/2019) is an author produced version of a paper published in ADDICTION BIOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

KW - nicotine

KW - insula

KW - striatum

U2 - 10.1111/adb.12679

DO - 10.1111/adb.12679

M3 - Article

SN - 1369-1600

JO - Addiction Biology

JF - Addiction Biology

ER -