title: Individual differences in amygdala reactivity following nicotinic receptor stimulation in abstinent smokers.
abstract: Hyperactive amygdala functioning may underlie emotional dysregulation during smoking abstinence and represents one neurobiological target for pharmacological cessation aids. Available pharmacotherapies (e.g., nicotine replacement and varenicline) aid only a subset of individuals with smoking cessation and therefore elucidating the neurobiological impact of these medications is critical to expedite improved interventions. In a fMRI study employing a within-subject, double-blind, placebo-controlled design, we assessed task performance and amygdala functioning during an emotional face matching paradigm following administration of nicotine and varenicline to 24 abstinent smokers and 20 nonsmokers. All participants underwent ~17days of varenicline and placebo pill administration and were scanned, on different days under each condition, wearing a transdermal nicotine or placebo patch. During the amygdala reactivity paradigm, nicotinic acetylcholine receptor (nAChR) stimulation by nicotine and varenicline decreased reaction time (RT) in abstinent smokers but not in nonsmokers. When considering all smokers as a single homogenous group, no drug-induced effects on amygdala reactivity were detected. However, in an exploratory analysis we parsed participants into subgroups according to individual differences in the propensity to demonstrate stable performance augmentation following nAChR stimulation (stable RT-improvers [SI] vs. variable RT-improvers [VI]). Using this exploratory approach, drugs appeared to modulate amygdala reactivity in only one smoker subgroup but not in either nonsmoker subgroup. Specifically, in the SI-smoker cohort abstinence-induced elevated amygdala reactivity was down-regulated by nAChR stimulation. In contrast, varenicline and nicotine did not modulate amygdala functioning in the VI-smoker cohort who displayed moderate levels of amygdala reactivity in the absence of drug administration. These results suggest that pharmacotherapies most robustly dampened amygdala functioning in smokers appearing susceptible to abstinence-induced effects. Such findings provide a step towards fractionating the smoker phenotype by discrete neurobiological characteristics.
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD, USA. Electronic address: masuther@fiu.edu.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Sutherland
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD, USA.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Carroll
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD, USA.
authors.forename: Betty Jo
authors.initials: BJ
authors.lastname: Salmeron
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ross
authors.affiliation: University of Maryland School of Medicine, Maryland Psychiatric Research Center, Department of Psychiatry, Baltimore, MD, USA.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH/DHHS, Baltimore, MD, USA.
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D001552:Benzazepines / Q000627:therapeutic use; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D016540:Smoking Cessation / Q000379:methods*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D061485:Tobacco Use Cessation Devices; D000068580:Varenicline; D055815:Young Adult
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D000068580:Varenicline
keywords: Amygdala; Emotion; Functional magnetic resonance imaging (fMRI); Nicotine; Varenicline; Withdrawal