title: Open label smoking cessation with varenicline is associated with decreased glutamate levels and functional changes in anterior cingulate cortex: preliminary findings.
abstract: BACKGROUND
  Varenicline, the most effective single agent for smoking cessation, is a partial agonist at α4β2 nicotinic acetylcholine receptors. Increasing evidence implicates glutamate in the pathophysiology of addiction and one of the benefits of treatment for smoking cessation is the ability to regain cognitive control.
  
  
  OBJECTIVE
  To evaluate the effects of 12-week varenicline administration on glutamate levels in the dorsal anterior cingulate cortex (dACC) and functional changes within the cognitive control network.
  
  
  METHODS
  We used single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) in the dACC and functional MRI (fMRI) during performance of a Stroop color-naming task before and after smoking cessation with varenicline in 11 healthy smokers (open label design). Using the dACC as a seed region, we evaluated functional connectivity changes using a psychophysiological interaction (PPI) analysis.
  
  
  RESULTS
  We observed a significant decrease in dACC glutamate + glutamine (Glx)/Cr levels as well as significant blood oxygen level-dependent signal (BOLD) decreases in the rostral ACC/medial orbitofrontal cortex and precuneus/posterior cingulate cortex. These BOLD changes are suggestive of alterations in default mode network (DMN) function and are further supported by the results of the PPI analysis that revealed changes in connectivity between the dACC and regions of the DMN. Baseline measures of nicotine dependence and craving positively correlated with baseline Glx/Cr levels.
  
  
  CONCLUSIONS
  These results suggest possible mechanisms of action for varenicline such as reduction in Glx levels in dACC and shifts in BOLD connectivity between large scale brain networks. They also suggest a role for ACC Glx in the modulation of behavior. Due to the preliminary nature of this study (lack of control group and small sample size), future studies are needed to replicate these findings.
authors: Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham Birmingham, AL, USA ; Department of Psychology, Behavioral Neuroscience, The University of Alabama at Birmingham Birmingham, AL, USA.
authors: Muriah D
authors: MD
authors: Wheelock
authors: Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham Birmingham, AL, USA ; Department of Biomedical Engineering, The University of Alabama at Birmingham Birmingham, AL, USA.
authors: Meredith A
authors: MA
authors: Reid
authors: Department of Biomedical Engineering, The University of Alabama at Birmingham Birmingham, AL, USA.
authors: Harrison
authors: H
authors: To
authors: Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham Birmingham, AL, USA.
authors: David M
authors: DM
authors: White
authors: Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham Birmingham, AL, USA.
authors: Karen L
authors: KL
authors: Cropsey
authors: Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham Birmingham, AL, USA.
authors: Adrienne C
authors: AC
authors: Lahti
keywords: MRS; PPI; addiction; connectivity; fMRI; nicotine; smoking; varenicline