The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study

Drug and Alcohol Dependence

Volumn 156, Issue , 2015, Pages 234-242

  Froeliger, B ^a,b   McConnell, P A ^a   Stankeviciute, N ^a   McClure, E A ^a   Kalivas, P W ^a   Gray, K M ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Accumbens; Cigarette; Cingulate; Glutamate; Nicotine; RsFC

Indexed keywords

ACETYLCYSTEINE; PLACEBO;

ADULT; ARTICLE; CEREBELLUM; CLINICAL ARTICLE; CONTROLLED STUDY; CORPUS STRIATUM; DEFAULT MODE NETWORK; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; FRONTOSTRIATUM; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GASTROESOPHAGEAL REFLUX; HUMAN; MALE; MEDIAL FRONTAL CORTEX; MOOD CHANGE; NAUSEA; NEUROTRANSMISSION; OUTCOME ASSESSMENT; PILOT STUDY; PRECUNEUS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESTING STATE NETWORK; REWARD; SMOKING CESSATION; SUBSTANCE ABUSE; TOBACCO DEPENDENCE; VENTRAL STRIATUM; WITHDRAWAL SYNDROME; DRUG EFFECTS; FRONTAL LOBE; MIDDLE AGED; NERVE TRACT; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; TOBACCO USE DISORDER;

ACETYLCYSTEINE; ADULT; CORPUS STRIATUM; DOUBLE-BLIND METHOD; FEMALE; FRONTAL LOBE; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; NEURAL PATHWAYS; PILOT PROJECTS; SMOKING CESSATION; SUBSTANCE WITHDRAWAL SYNDROME; TOBACCO USE DISORDER;

EID: 84946411440     PISSN: 03768716     EISSN: 18790046     Source Type: Journal    
DOI: 10.1016/j.drugalcdep.2015.09.021     Document Type: Article

References (89)

1. AHA, Lloyd-Jones D., Adams R.J., Brown T.M., Carnethon M., Dai S., De Simone G., Ferguson T.B., Ford E., Furie K., Gillespie C., Go A., Greenlund K., Haase N., Hailpern S., Ho P.M., Howard V., Kissela B., Kittner S., Lackland D., Lisabeth L., Marelli A., McDermott M.M., Meigs J., Mozaffarian D., Mussolino M., Nichol G., Roger V.L., Rosamond W., Sacco R., Sorlie P., Stafford R., Thom T., Wasserthiel-Smoller S., Wong N.D., Wylie-Rosett J. Heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation 2010, 121:e46-e215. AHA Committee, Stroke Statistics Subcommittee.
2. Akkus F., Ametamey S.M., Treyer V., Burger C., Johayem A., Umbricht D., Gomez Mancilla B., Sovago J., Buck A., Hasler G. Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [11C]ABP688 positron emission tomography. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:737-742.
3. Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage 2007, 38:95-113.
4. Augustus Diggs H., Froeliger B., Carlson J.M., Gilbert D.G. Smoker-nonsmoker differences in neural response to smoking-related and affective cues: an fMRI investigation. Psychiatry Res. 2013, 211:85-87.
5. Azizian A., Nestor L.J., Payer D., Monterosso J.R., Brody A.L., London E.D. Smoking reduces conflict-related anterior cingulate activity in abstinent cigarette smokers performing a Stroop task. Neuropsychopharmacology 2010, 35:775-782.
6. Baker D.A., McFarland K., Lake R.W., Shen H., Toda S., Kalivas P.W. N-acetyl cysteine-induced blockade of cocaine-induced reinstatement. Ann. N. Y. Acad. Sci. 2003, 1003:349-351.
7. Bastian A.J. Learning to predict the future: the cerebellum adapts feedforward movement control. Curr. Opin. Neurobiol. 2006, 16:645-649.
8. Bell R.P., Garavan H., Foxe J.J. Neural correlates of craving and impulsivity in abstinent former cocaine users: towards biomarkers of relapse risk. Neuropharmacology 2014, 85:461-470.
9. Berglind W.J., Whitfield T.W., LaLumiere R.T., Kalivas P.W., McGinty J.F. A single intra-PFC infusion of BDNF prevents cocaine-induced alterations in extracellular glutamate within the nucleus accumbens. J. Neurosci. 2009, 29:3715-3719.
10. Berk M., Malhi G.S., Gray L.J., Dean O.M. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol. Sci. 2013, 34:167-177.
11. Berridge K.C., Robinson T.E., Aldridge J.W. Dissecting components of reward: 'liking', 'wanting', and learning. Curr. Opin. Pharmacol. 2009, 9:65-73.
12. Biswal B., Yetkin F.Z., Haughton V.M., Hyde J.S. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn. Reson. Med. 1995, 34:537-541.
13. Broadbent D.E., Cooper P.F., FitzGerald P., Parkes K.R. The Cognitive Failures Questionnaire (CFQ) and its correlates. Br. J. Clin. Psychol. 1982, 21(Pt 1):1-16.
14. Brody A.L., Mandelkern M.A., London E.D., Childress A.R., Lee G.S., Bota R.G., Ho M.L., Saxena S., Baxter L.R., Madsen D., Jarvik M.E. Brain metabolic changes during cigarette craving. Arch. Gen. Psychiatry 2002, 59:1162-1172.
15. Cahill K., Stevens S., Perera R., Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst. Rev. 2013, 5:CD009329.
16. CDC annual smoking-attributable mortality, years of potential life lost, and productivity losses-United States, 1995-1999. MMWR 2002, 51:300-313.
17. Cook J.W., Spring B., McChargue D., Hedeker D. Hedonic capacity, cigarette craving, and diminished positive mood. Nicotine Tob. Res. 2004, 6:39-47.
18. Doya K. Complementary roles of basal ganglia and cerebellum in learning and motor control. Curr. Opin. Neurobiol. 2000, 10:732-739.
19. Dringen R., Gutterer J.M., Gros C., Hirrlinger J. Aminopeptidase N mediates the utilization of the GSH precursor CysGly by cultured neurons. J. Neurosci. Res. 2001, 66:1003-1008.
20. Duncan N.W., Wiebking C., Tiret B., Marjanska M., Hayes D.J., Lyttleton O., Doyon J., Northoff G. Glutamate concentration in the medial prefrontal cortex predicts resting-state cortical-subcortical functional connectivity in humans. PLOS ONE 2013, 8:e60312.
21. Friston K.J., Jezzard P., Turner R. Analysis of functional MRI time-series. Hum. Brain Mapp. 1994, 1:153-171.
22. Froeliger B., Crowell Beckham J., Feldman Dennis M., Victoria Kozink R., Joseph McClernon F. Effects of nicotine on emotional reactivity in PTSD and Non-PTSD smokers: results of a pilot fMRI Study. Adv. Pharmacol. Sci. 2012, 2012:265724.
23. Froeliger B., Modlin L., Wang L., Kozink R.V., McClernon F.J. Nicotine withdrawal modulates frontal brain function during an affective Stroop task. Psychopharmacology (Berl.) 2012, 220:707-718.
24. Froeliger B., Modlin L.A., Kozink R.V., Wang L., Garland E.L., Addicott M.A., McClernon F.J. Frontoparietal attentional network activation differs between smokers and nonsmokers during affective cognition. Psychiatry Res. 2013, 211:57-63.
25. Froeliger B., Modlin L.A., Kozink R.V., Wang L., McClernon F.J. Smoking abstinence and depressive symptoms modulate the executive control system during emotional information processing. Addict. Biol. 2012, 17:668-679.
26. Garland E.L., Froeliger B., Howard M.O. Mindfulness training targets neurocognitive mechanisms of addiction at the attention-appraisal-emotion interface. Front. Psychiatry 2014, 4:173.
27. Gipson C.D., Reissner K.J., Kupchik Y.M., Smith A.C., Stankeviciute N., Hensley-Simon M.E., Kalivas P.W. Reinstatement of nicotine seeking is mediated by glutamatergic plasticity. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:9124-9129.
28. Goldman M., Szucs-Reed R.P., Jagannathan K., Ehrman R.N., Wang Z., Li Y., Suh J.J., Kampman K., O'Brien C.P., Childress A.R., Franklin T.R. Reward-related brain response and craving correlates of marijuana cue exposure: a preliminary study in treatment-seeking marijuana-dependent subjects. J. Addict. Med. 2013, 7:8-16.
29. Goldstein R.Z., Volkow N.D. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am. J. Psychiatry 2002, 159:1642-1652.
30. Gonzales D., Rennard S.I., Nides M., Oncken C., Azoulay S., Billing C.B., Watsky E.J., Gong J., Williams K.E., Reeves K.R. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006, 296:47-55. Varenicline Phase 3 Study G.
31. Gray K.M., Watson N.L., Carpenter M.J., Larowe S.D. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am. J. Addict. 2010, 19:187-189.
32. Heatherton T.F., Kozlowski L.T., Frecker R.C., Fagerstrom K.O. The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br. J. Addict. 1991, 86:1119-1127.
33. Hong L.E., Gu H., Yang Y., Ross T.J., Salmeron B.J., Buchholz B., Thaker G.K., Stein E.A. Association of nicotine addiction and nicotine's actions with separate cingulate cortex functional circuits. Arch. Gen. Psychiatry 2009, 66:431-441.
34. Huang W., King J.A., Ursprung W., Zheng S., Zhang N., Kennedy D.N., Ziedonis D., DiFranza J.R. The development and expression of physical nicotine dependence corresponds to structural and functional alterations in the anterior cingulate-precuneus pathway. Brain Behav. 2014, 4:408-417.
35. Huang Z., Davis Iv H., Yue Q., Wiebking C., Duncan N.W., Zhang J., Wagner N.F., Wolff A., Northoff G. Increase in glutamate/glutamine concentration in the medial prefrontal cortex during mental imagery: a combined functional mrs and fMRI study. Hum. Brain Mapp. 2015, 36:3204-3212.
36. Janes A.C., Pizzagalli D.A., Richardt S., de B.F.B., Chuzi S., Pachas G., Culhane M.A., Holmes A.J., Fava M., Evins A.E., Kaufman M.J. Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biol. Psychiatry 2010, 67:722-729.
37. Jasinska A.J., Stein E.A., Kaiser J., Naumer M.J., Yalachkov Y. Factors modulating neural reactivity to drug cues in addiction: a survey of human neuroimaging studies. Neurosci. Biobehav. Rev. 2014, 38:1-16.
38. Jorenby D.E., Hays J.T., Rigotti N.A., Azoulay S., Watsky E.J., Williams K.E., Billing C.B., Gong J., Reeves K.R. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006, 296:56-63.
39. Kalivas P.W. The glutamate homeostasis hypothesis of addiction. Nat. Rev. Neurosci. 2009, 10:561-572.
40. Kilts C.D., Gross R.E., Ely T.D., Drexler K.P. The neural correlates of cue-induced craving in cocaine-dependent women. Am. J. Psychiatry 2004, 161:233-241.
41. Knackstedt L.A., LaRowe S., Mardikian P., Malcolm R., Upadhyaya H., Hedden S., Markou A., Kalivas P.W. The role of cystine-glutamate exchange in nicotine dependence in rats and humans. Biol. Psychiatry 2009, 65:841-845.
42. Knutson B., Adams C.M., Fong G.W., Hommer D. Anticipation of increasing monetary reward selectively recruits nucleus accumbens. J. Neurosci. 2001, 21:RC159.
43. Knutson B., Gibbs S.E. Linking nucleus accumbens dopamine and blood oxygenation. Psychopharmacology (Berl.) 2007, 191:813-822.
44. Knutson B., Westdorp A., Kaiser E., Hommer D. FMRI Visualization of brain activity during a monetary incentive delay task. Neuroimage 2000, 12:20-27.
45. Kober H., Mende-Siedlecki P., Kross E.F., Weber J., Mischel W., Hart C.L., Ochsner K.N. Prefrontal-striatal pathway underlies cognitive regulation of craving. Proc. Natl. Acad. Sci. 2010, 107:14811-14816.
46. Koob G.F., Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 2001, 24:97-129.
47. Koob G.F., Le Moal M. Neurobiological mechanisms for opponent motivational processes in addiction. Philos. Trans. R. Soc. B. Biol. Sci. 2008, 363:3113-3123.
48. Kozink R.V., Lutz A.M., Rose J.E., Froeliger B., McClernon F.J. Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition. Addict. Biol. 2010, 15:480-490.
49. Kufahl P.R., Li Z., Risinger R.C., Rainey C.J., Wu G., Bloom A.S., Li S.J. Neural responses to acute cocaine administration in the human brain detected by fMRI. Neuroimage 2005, 28:904-914.
50. Kupchik Y.M., Moussawi K., Tang X.C., Wang X., Kalivas B.C., Kolokithas R., Ogburn K.B., Kalivas P.W. The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine. Biol. Psychiatry 2012, 71:978-986.
51. LaRowe S.D., Mardikian P., Malcolm R., Myrick H., Kalivas P., McFarland K., Saladin M., McRae A., Brady K. Safety and tolerability of N-acetylcysteine in cocaine-dependent individuals. Am. J. Addict. 2006, 15:105-110.
52. Lewerenz J., Hewett S.J., Huang Y., Lambros M., Gout P.W., Kalivas P.W., Massie A., Smolders I., Methner A., Pergande M., Smith S.B., Ganapathy V., Maher P. The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antiox. Redox Signal. 2013, 18:522-555.
53. Li Q., Wang Y., Zhang Y., Li W., Yang W., Zhu J., Wu N., Chang H., Zheng Y., Qin W., Zhao L., Yuan K., Liu J., Wang W., Tian J. Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: an event-related fMRI study. Brain Res. 2012, 1469:63-72.
54. Ma N., Liu Y., Li N., Wang C.-X., Zhang H., Jiang X.-F., Xu H.-S., Fu X.-M., Hu X., Zhang D.-R. Addiction related alteration in resting-state brain connectivity. Neuroimage 2010, 49:738-744.
55. Manjón J.V., Coupé P., Martí-Bonmatí L., Collins D.L., Robles M. Adaptive non-local means denoising of MR images with spatially varying noise levels. J. Magn. Reson. Imag. 2010, 31:192-203.
56. Mardikian P.N., LaRowe S.D., Hedden S., Kalivas P.W., Malcolm R.J. An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study. Prog. Neuropsychopharmacol. Biol. Psychiatry 2007, 31:389-394.
57. Matthews S.C., Simmons A.N., Lane S.D., Paulus M.P. Selective activation of the nucleus accumbens during risk-taking decision making. Neuroreport 2004, 15:2123-2127.
58. McClernon F.J., Hiott F.B., Huettel S.A., Rose J.E. Abstinence-induced changes in self-report craving correlate with event-related fMRI responses to smoking cues. Neuropsychopharmacology 2005, 30:1940-1947.
59. McClernon F.J., Kozink R.V., Lutz A.M., Rose J.E. 24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum. Psychopharmacology (Berl.) 2009, 204:25-35.
60. McClure E.A., Baker N.L., Gipson C.D., Carpenter M.J., Roper A.P., Froeliger B.E., Kalivas P.W., Gray K.M. An open-label pilot trial of N-acetylcysteine and varenicline in adult cigarette smokers. Am. J. Drug Alcohol Abuse 2014, 41:52-56.
61. McClure E.A., Gipson C.D., Malcolm R.J., Kalivas P.W., Gray K.M. potential role of n-acetylcysteine in the management of substance use disorders. CNS Drugs 2014, 28:95-106.
62. Moreno-López L., Perales J.C., Son D., Albein-Urios N., Soriano-Mas C., Martinez-Gonzalez J.M., Wiers R.W., Verdejo-García A. Cocaine use severity and cerebellar gray matter are associated with reversal learning deficits in cocaine-dependent individuals. Addict. Biol. 2015, 20:546-556.
63. Motzkin J.C., Baskin-Sommers A., Newman J.P., Kiehl K.A., Koenigs M. Neural correlates of substance abuse: reduced functional connectivity between areas underlying reward and cognitive control. Hum. Brain Mapp. 2014, 35:4282-4292.
64. Moussawi K., Pacchioni A., Moran M., Olive M.F., Gass J.T., Lavin A., Kalivas P.W. N-Acetylcysteine reverses cocaine-induced metaplasticity. Nat. Neurosci. 2009, 12:182-189.
65. Oncken C., Gonzales D., Nides M., Rennard S., Watsky E., Billing C.B., Anziano R., Reeves K. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch. Intern. Med. 2006, 166:1571-1577.
66. Pierce R.C., Bell K., Duffy P., Kalivas P.W. Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J. Neurosci. 1996, 16:1550-1560.
67. Prado E., Maes M., Piccoli L.G., Baracat M., Barbosa D.S., Franco O., Dodd S., Berk M., Vargas Nunes S.O. N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study. Redox Rep. 2015, 20:215-222.
68. Radloff L.S. The CES-D scale: a self report depression scale for research in the general population. Appl. Psychol. Measure. 1977, 1:385-401.
69. Rajapakse J.C., Giedd J.N., Rapoport J.L. Statistical approach to segmentation of single-channel cerebral MR images. IEEE Trans. Med. Imaging 1997, 16:176-186.
70. Reichel C.M., Moussawi K., Do P.H., Kalivas P.W., See R.E. Chronic N-acetylcysteine during abstinence or extinction after cocaine self-administration produces enduring reductions in drug seeking. J. Pharmacol. Exp. Ther. 2011, 337:487-493.
71. Reissner K.J., Kalivas P.W. Using glutamate homeostasis as a target for treating addictive disorders. Behav. Pharmacol. 2010, 21:514-522.
72. Risinger R.C., Salmeron B.J., Ross T.J., Amen S.L., Sanfilipo M., Hoffmann R.G., Bloom A.S., Garavan H., Stein E.A. Neural correlates of high and craving during cocaine self-administration using BOLD fMRI. Neuroimage 2005, 26:1097-1108.
73. Rogers R.D., Ramnani N., Mackay C., Wilson J.L., Jezzard P., Carter C.S., Smith S.M. Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition. Biol. Psychiatry 2004, 55:594-602.
74. Rushworth M.F., Buckley M.J., Behrens T.E., Walton M.E., Bannerman D.M. Functional organization of the medial frontal cortex. Curr. Opin. Neurobiol. 2007, 17:220-227.
75. Schmaal L., Berk L., Hulstijn K.P., Cousijn J., Wiers R.W., van den Brink W. Efficacy of N-acetylcysteine in the treatment of nicotine dependence: a double-blind placebo-controlled pilot study. Eur. Addict. Res. 2011, 17:211-216.
76. Schmaal L., Veltman D.J., Nederveen A., van den Brink W., Goudriaan A.E. N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients: a randomized crossover magnetic resonance spectroscopy study. Neuropsychopharmacology 2012, 37:2143-2152.
77. Shiffman S., Paty J.A., Gnys M., Kassel J.A., Hickcox M. First lapses to smoking: within-subjects analysis of real-time reports. J. Consult. Clin. Psychol. 1996, 64:366-379.
78. Shiffman S.M., Jarvik M.E. Smoking withdrawal symptoms in two weeks of abstinence. Psychopharmacology 1976, 50:35-39.
79. Shmuel A., Leopold D.A. Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: implications for functional connectivity at rest. Hum. Brain Mapp. 2008, 29:751-761.
80. Stolerman I.P., Jarvis M.J. The scientific case that nicotine is addictive. Psychopharmacology (Berl.) 1995, 117:2-10. discussion 14-20.
81. Taylor R.C., Harris N.A., Singleton E.G., Moolchan E.T., Heishman S.J. Tobacco craving: intensity-related effects of imagery scripts in drug abusers. Exp. Clin. Psychopharmacol. 2000, 8:75.
82. Tohka J., Zijdenbos A., Evans A. Fast and robust parameter estimation for statistical partial volume models in brain MRI. Neuroimage 2004, 23:84-97.
83. Tzvi E., Münte T.F., Krämer U.M. Delineating the cortico-striatal-cerebellar network in implicit motor sequence learning. Neuroimage 2014, 94:222-230.
84. Volkow N.D., Wang G.J., Fowler J.S., Logan J., Gatley S.J., Hitzemann R., Chen A.D., Dewey S.L., Pappas N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature 1997, 386:830-833.
85. Wang Z., Faith M., Patterson F., Tang K., Kerrin K., Wileyto E.P., Detre J.A., Lerman C. Neural substrates of abstinence-induced cigarette cravings in chronic smokers. J. Neurosci. 2007, 27:14035-14040.
86. Watson D., Clark L.A., Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J. Pers. Soc. Psychol. 1988, 54:1063-1070.
87. Westman E.C., Behm F.M., Simel D.L., Rose J.E. Smoking behavior on the first day of a quit attempt predicts long-term abstinence. Arch. Intern. Med. 1997, 157:335-340.
88. Wilson S.J., Sayette M.A. Neuroimaging craving: urge intensity matters. Addiction 2014, 110:195-203.
89. Zink C.F., Pagnoni G., Martin M.E., Dhamala M., Berns G.S. Human striatal response to salient nonrewarding stimuli. J. Neurosci. 2003, 23:8092-8097.