title: The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.
abstract: BACKGROUND
  Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period.
  
  
  METHODS
  The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning.
  
  
  RESULTS
  As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]).
  
  
  CONCLUSIONS
  Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, United States; Hollings Cancer Center, Medical University of South Carolina, United States; Department of Psychiatry, Medical University of South Carolina, United States. Electronic address: froelige@musc.edu.
authors.forename: B
authors.initials: B
authors.lastname: Froeliger
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, United States.
authors.forename: P A
authors.initials: PA
authors.lastname: McConnell
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, United States.
authors.forename: N
authors.initials: N
authors.lastname: Stankeviciute
authors.affiliation: Department of Psychiatry, Medical University of South Carolina, United States.
authors.forename: E A
authors.initials: EA
authors.lastname: McClure
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, United States.
authors.forename: P W
authors.initials: PW
authors.lastname: Kalivas
authors.affiliation: Department of Psychiatry, Medical University of South Carolina, United States.
authors.forename: K M
authors.initials: KM
authors.lastname: Gray
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects* / Q000503:physiopathology*; D010865:Pilot Projects; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014029:Tobacco Use Disorder / Q000503:physiopathology* / Q000534:rehabilitation*
chemical_list: D000111:Acetylcysteine
keywords: Accumbens; Cigarette; Cingulate; Glutamate; Nicotine; rsFC