본문 바로가기
KERD
논문KCI 등재

Baclofen-induced Changes in the Resting Brain Modulate Smoking Cue Reactivity: A Double-blind Placebo-controlled Functional Magnetic Resonance Imaging Study in Cigarette Smokers

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure. Methods: In this longitudinal, double blind, placebo-controlled neuropharmacological study 43 non-abstinent, sated treatment-seeking cigarette smokers (63% male) participated in an fMRI resting-state scan and a SC-reactivity task prior to (T1) and 3 weeks following randomization (T2; baclofen: 80 mg/day; n = 21). Subjective craving reports were acquired before and after SC exposure to explicitly examine SC-induced craving. Results: Whole-brain full-factorial analysis revealed a group-by-time interaction with greater resting brain activation of the right dorsolateral prefrontal cortex (dlPFC) at T2 in the baclofen group (BAC) (pFWEcorr = 0.02), which was associated with reduced neural responses to SCs in key cue-reactive brain regions; the anterior ventral insula and ventromedial prefrontal cortex (pFWEcorr < 0.01). BAC, but not the placebo group reported decreased SC-elicited craving (p = 0.02). Conclusion: Results suggest that baclofen mitigates the reward response to SCs through an increase in tonic activation of the dlPFC, an executive control region. Through these mechanisms, baclofen may offer SC-vulnerable smokers protection from SC-induced relapse.

Abstract

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure. Methods: In this longitudinal, double blind, placebo-controlled neuropharmacological study 43 non-abstinent, sated treatment-seeking cigarette smokers (63% male) participated in an fMRI resting-state scan and a SC-reactivity task prior to (T1) and 3 weeks following randomization (T2; baclofen: 80 mg/day; n = 21). Subjective craving reports were acquired before and after SC exposure to explicitly examine SC-induced craving. Results: Whole-brain full-factorial analysis revealed a group-by-time interaction with greater resting brain activation of the right dorsolateral prefrontal cortex (dlPFC) at T2 in the baclofen group (BAC) (pFWEcorr = 0.02), which was associated with reduced neural responses to SCs in key cue-reactive brain regions; the anterior ventral insula and ventromedial prefrontal cortex (pFWEcorr < 0.01). BAC, but not the placebo group reported decreased SC-elicited craving (p = 0.02). Conclusion: Results suggest that baclofen mitigates the reward response to SCs through an increase in tonic activation of the dlPFC, an executive control region. Through these mechanisms, baclofen may offer SC-vulnerable smokers protection from SC-induced relapse.

참고문헌 (85)

  1. WHO global report on trends in prevalence of tobacco smoking 2000-2025, "Commar A", World Health Organization, ~ (2018)
  2. Quitting smoking among adults—United States, 2000-2015. Morbidity and Mortality Weekly Report (MMWR), "Babb S", Centers for Disease Control and Prevention, ~ (2017)
  3. García-Rodríguez O, "Probability and predictors of relapse to smoking : results of the National Epidemiologic Survey on Alcohol and Related Conditions(NESARC)", Drug Alcohol Depend, 132, pp.479~485 (2013)
  4. Perkins KA, "Does smoking cue-induced craving tell us anything important about nicotine dependence?", Addiction, 104, pp.1610~1616 (2009)
  5. Carter BL, "Cue-reactivity and the future of addiction research", Addiction, 94, pp.349~351 (1999)
  6. Drummond DC, "What does cue-reactivity have to offer clinical research?", Addiction, 95(Suppl 2), pp.S129~S144 (2000)
  7. Tiffany ST, "The continuing conundrum of craving", Addiction, 104, pp.1618~1619 (2009)
  8. Bedi G, "Incubation of cue-induced cigarette craving during abstinence in human smokers", Biol Psychiatry, 69, pp.708~711 (2011)
  9. Franklin TR, "Limbic activation to cigarette smoking cues independent of nicotine withdrawal : a perfusion fMRI study", Neuropsychopharmacology, 32, pp.2301~2309 (2007)
  10. Conklin CA, "Examining the relationship between cue-induced craving and actual smoking", Exp Clin Psychopharmacol, 23, pp.90~96 (2015)
  11. Janes AC, "Revisiting the role of the insula and smoking cue-reactivity in relapse : a replication and extension of neuroimaging findings", Drug Alcohol Depend, 179, pp.8~12 (2017)
  12. Janes AC, "Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence", Biol Psychiatry, 67, pp.722~729 (2010)
  13. Versace F, "Prequit fMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome", Nicotine Tob Res, 16, pp.697~708 (2014)
  14. Wilkes S, "The use of bupropion SR in cigarette smoking cessation", Int J Chron Obstruct Pulmon Dis, 3, pp.45~53 (2008)
  15. Mihalak KB, "Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors", Mol Pharmacol, 70, pp.801~805 (2006)
  16. Rollema H, "Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid", Neuropharmacology, 52, pp.985~994 (2007)
  17. Ebbert JO, "Effect of varenicline on smoking cessation through smoking reduction : a randomized clinical trial", JAMA, 313, pp.687~694 (2015)
  18. Fadda P, "Baclofen antagonizes nicotine-, cocaine-, and morphine-induced dopamine release in the nucleus accumbens of rat", Synapse, 50, pp.1~6 (2003)
  19. Brebner K, "A potential role for GABA(B)agonists in the treatment of psychostimulant addiction", Alcohol Alcohol, 37, pp.478~484 (2002)
  20. Fattore L, "Baclofen prevents drug-induced reinstatement of extinguished nicotine-seeking behaviour and nicotine place preference in rodents", Eur Neuropsychopharmacol, 19, pp.487~498 (2009)
  21. Beck A, "Effects of high-dose baclofen on cue reactivity in alcohol dependence : a randomized, placebo-controlled pharmaco-fMRI study", Eur Neuropsychopharmacol, 28, pp.1206~1216 (2018)
  22. Warren B. Logge, "Baclofen attenuates fMRI alcohol cue reactivity in treatment-seeking alcohol dependent individuals", Psychopharmacology (2019), Springer Science and Business Media LLC[DOI]
  23. Young KA, "Nipping cue reactivity in the bud : baclofen prevents limbic activation elicited by subliminal drug cues", J Neurosci, 34, pp.5038~5043 (2014)
  24. Bharath Holla, "Brain Functional Magnetic Resonance Imaging Cue-reactivity Can Predict Baclofen Response in Alcohol Use Disorders", Clinical Psychopharmacology and Neuroscience, 16(3), pp.290~301 (2018), 대한정신약물학회[DOI]
  25. Franklin TR, "Modulation of resting brain cerebral blood flow by the GABA B agonist, baclofen : a longitudinal perfusion fMRI study", Drug Alcohol Depend, 117, pp.176~183 (2011)
  26. Franklin T, "Effects of varenicline on smoking cue−triggered neural and craving responses", Arch Gen Psychiatry, 68, pp.516~526 (2011)
  27. McHugh MJ, "Executive control network connectivity strength protects against relapse to cocaine use", Addict Biol, 22, pp.1790~1801 (2017)
  28. Zilverstand A, "Neuroimaging impaired response inhibition and salience attribution in human drug addiction : a systematic review", Neuron, 98, pp.886~903 (2018)
  29. Franklin TR, "Influence of menstrual cycle phase on neural and craving responses to appetitive smoking cues in naturally cycling females", Nicotine Tob Res, 17, pp.390~397 (2015)
  30. Dumais KM, "Multi-site exploration of sex differences in brain reactivity to smoking cues : consensus across sites and methodologies", Drug Alcohol Depend, 178, pp.469~476 (2017)
  31. Fagerstrom KO, "Measuring nicotine dependence : a review of the Fagerstrom Tolerance Questionnaire", J Behav Med, 12, pp.159~182 (1989)
  32. Sheehan DV, "The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10", J Clin Psychiatry, 59(Suppl 20), pp.22~33 (1998)
  33. Wechsler D, "WASI, Wechsler abbreviated scale of intelligence" (1999), Psychological Corporation
  34. Dill T, "Contraindications to magnetic resonance imaging : non-invasive imaging", Heart, 94, pp.943~948 (2008)
  35. Byrne JEM, "Time of day differences in neural reward functioning in healthy young men", J Neurosci, 37, pp.8895~8900 (2017)
  36. Wu WC, "A theoretical and experimental investigation of the tagging efficiency of pseudocontinuous arterial spin labeling", Magn Reson Med, 58, pp.1020~1027 (2007)
  37. Hermes M, "Reproducibility of continuous arterial spin labeling perfusion MRI after 7 weeks", MAGMA, 20, pp.103~115 (2007)
  38. Benowitz NL, "Cardiovascular toxicity of nicotine : implications for nicotine replacement therapy", J Am Coll Cardiol, 29, pp.1422~1431 (1997)
  39. Wilson SJ, "Carry-over effects of smoking cue exposure on working memory performance", Nicotine Tob Res, 9, pp.613~619 (2007)
  40. Wetherill RR, "The impact of sex on brain responses to smoking cues : a perfusion fMRI study", Biol Sex Differ, 4, pp.9~ (2013)
  41. Wang Z, "Empirical optimization of ASL data analysis using an ASL data processing toolbox : ASLtbx", Magn Reson Imaging, 26, pp.261~269 (2008)
  42. FMRIB Analysis Group, "The manual of FMRIB software library", FMRIB Analysis Group, ~ (2018)
  43. MathWorks Inc, "The manual of Statistics and machine learning toolbox-release 2016a", MathWorks Inc, ~ (2016)
  44. Wang Z, "Improving cerebral blood flow quantification for arterial spin labeled perfusion MRI by removing residual motion artifacts and global signal fluctuations", Magn Reson Imaging, 30, pp.1409~1415 (2012)
  45. Greve DN, "Accurate and robust brain image alignment using boundary-based registration", Neuroimage, 48, pp.63~72 (2009)
  46. Dolui S, "Comparison of PASL, PCASL, and background-suppressed 3D PCASL in mild cognitive impairment", Hum Brain Mapp, 38, pp.5260~5273 (2017)
  47. Alsop DC, "Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications : a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia", Magn Reson Med, 73, pp.102~116 (2015)
  48. Dolui S, "Structural Correlation-based Outlier Rejection(SCORE)algorithm for arterial spin labeling time series", J Magn Reson Imaging, 45, pp.1786~1797 (2017)
  49. Dolui S, "SCRUB: a structural correlation and empirical robust bayesian method for ASL data", ISMRM 25th Annual Meeting and Exhibition (2016)
  50. Dolui S, "Automated quality evaluation index for 2D ASL CBF maps", ISMRM 25th Annual Meeting and Exhibition (2017)
  51. "R: a language and environment for statistical computing" (2017)[URL]
  52. Bredlau AL, "Neurocognitive changes after sustained ketamine administration in children with chronic pain", J Palliat Care Med, 5, pp.215~ (2015)
  53. Abdi H, "The Bonferonni and Šidák corrections for multiple comparisons", 9~ (2007)
  54. Blakesley RE, "Comparisons of methods for multiple hypothesis testing in neuropsychological research", Neuropsychology, 23, pp.255~264 (2009)
  55. Lancaster JL, "Automated regional behavioral analysis for human brain images", Front Neuroinform, 6, pp.23~ (2012)
  56. Wetherill RR, "Sex differences in associations between cannabis craving and neural responses to cannabis cues : Implications for treatment", Exp Clin Psychopharmacol, 23, pp.238~246 (2015)
  57. Dumais KM, "Multi-site exploration of sex differences in brain reactivity to smoking cues : consensus across sites and methodologies", Drug Alcohol Depend, 178, pp.469~476 (2017)
  58. Wasserstein RL, "The ASA statement on p-values : context, process, and purpose", Am Stat, 70, pp.129~133 (2016)
  59. Lindquist MA, "Zen and the art of multiple comparisons", Psychosom Med, 77, pp.114~125 (2015)
  60. Zelle SL, "The first day is always the hardest : Functional connectivity during cue exposure and the ability to resist smoking in the initial hours of a quit attempt", Neuroimage, 151, pp.24~32 (2017)
  61. Schluter RS, "Effects of non-invasive neuromodulation on executive and other cognitive functions in addictive disorders : a systematic review", Front Neurosci, 12, pp.642~ (2018)
  62. Karch S, "Real-time fMRI neurofeedback in patients with tobacco use disorder during smoking cessation : functional differences and implications of the first training session in regard to future abstinence or relapse", Front Hum Neurosci, 13, pp.65~ (2019)
  63. Clarke PJ, "The causal role of the dorsolateral prefrontal cortex in the modification of attentional bias : evidence from transcranial direct current stimulation", Biol Psychiatry, 76, pp.946~952 (2014)
  64. McBride D, "Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers : an fMRI study", Neuropsychopharmacology, 31, pp.2728~2738 (2006)
  65. Lee JH, "A functional magnetic resonance imaging(FMRI)study of cue-induced smoking craving in virtual environments", Appl Psychophysiol Biofeedback, 30, pp.195~204 (2005)
  66. Naqvi NH, "The insula and drug addiction : an interoceptive view of pleasure, urges, and decision-making", Brain Struct Funct, 214, pp.435~450 (2010)
  67. Claus ED, "Association between nicotine dependence severity, BOLD response to smoking cues, and functional connectivity", Neuropsychopharmacology, 38, pp.2363~2372 (2013)
  68. Janes AC, "Memory retrieval of smoking-related images induce greater insula activation as revealed by an fMRI-based delayed matching to sample task", Addict Biol, 20, pp.349~356 (2015)
  69. Duerden EG, "Lateralization of affective processing in the insula", Neuroimage, 78, pp.159~175 (2013)
  70. Janes AC, "An increase in tobacco craving is associated with enhanced medial prefrontal cortex network coupling", PLoS One, 9, pp.e88228~ (2014)
  71. Kaller CP, "Dissociable contributions of left and right dorsolateral prefrontal cortex in planning", Cereb Cortex, 21, pp.307~317 (2011)
  72. DeWitt SJ, "The hyper-sentient addict : an exteroception model of addiction", Am J Drug Alcohol Abuse, 41, pp.374~381 (2015)
  73. Franklin TR, "DAT genotype modulates brain and behavioral responses elicited by cigarette cues", Neuropsychopharmacology, 34, pp.717~728 (2009)
  74. Addolorato G, "Dose-response effect of baclofen in reducing daily alcohol intake in alcohol dependence : secondary analysis of a randomized, double-blind, placebo-controlled trial", Alcohol Alcohol, 46, pp.312~317 (2011)
  75. Agabio R, "Baclofen for the treatment of alcohol use disorder : the Cagliari Statement", Lancet Psychiatry, 5, pp.957~960 (2018)
  76. de Beaurepaire R, "The use of baclofen as a treatment for alcohol use disorder : a clinical practice perspective", Front Psychiatry, 9, pp.708~ (2019)
  77. West R, "Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms, and rewarding effects of smoking during a quit attempt", Psychopharmacology(Berl), 197, pp.371~377 (2008)
  78. Brandon TH, "Varenicline effects on craving, cue reactivity, and smoking reward", Psychopharmacology(Berl), 218, pp.391~403 (2011)
  79. Ray LA, "The effects of varenicline on stress-induced and cue-induced craving for cigarettes", Drug Alcohol Depend, 131, pp.136~142 (2013)
  80. Ghanavatian S, "Baclofen" (2019), StatPearls Publishing
  81. "Baclofen" (2018)[URL]
  82. Franklin TR, "The GABA B agonist baclofen reduces cigarette consumption in a preliminary double-blind placebocontrolled smoking reduction study", Drug Alcohol Depend, 103, pp.30~36 (2009)
  83. Leggio L, "A preliminary double-blind, placebo-controlled randomized study of baclofen effects in alcoholic smokers", Psychopharmacology(Berl), 232, pp.233~243 (2015)
  84. Marsot A, "High variability in the exposure of baclofen in alcohol-dependent patients", Alcohol Clin Exp Res, 38, pp.316~321 (2014)
  85. Westerink BH, "The pharmacology of mesocortical dopamine neurons : a dual-probe microdialysis study in the ventral tegmental area and prefrontal cortex of the rat brain", J Pharmacol Exp Ther, 285, pp.143~154 (1998)

관련 논문AI추천

Brain Functional Magnetic Resonance Imaging Cue-reactivity Can Predict Baclofen Response in Alcohol Use DisordersBharath Holla, Biju Viswanath, Deepak Jayarajan, Ganesan Venkatasubramanian, Jitendriya Biswal, Rose Dawn Bharath, Sheshachala Karthik, Vivek Benegal대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2018 · 제16권 제3호Cue-induced Magnetic Resonance Spectroscopy of Glutamate in Addiction Research: Current Evidence, Pros, and ConsChun-Chia Kung, Li-Chung Huang, Muhammad Abdullah, Muhammad Imran Khan, Shih-Hsien Lin, Yen Kuang Yang대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2025 · 제23권 제3호Effect of Intensified Transcranial Direct-current Stimulation Targeting Bilateral Dorsolateral Prefrontal Cortex on Craving Reduction in Patients with Opioid (Heroin) Use DisorderAlireza Noroozi, Hadis Amini Tameh, Jaber Alizadehgoradel, Saeed Imani대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2024 · 제22권 제3호Scientific Evidence for the Addictiveness of Tobacco and Smoking Cessation in Tobacco Litigation노성원대한예방의학회 · 예방의학회지2018 · 제51권 제1호Anterior cingulate cortex and amygdala dysfunction among patients with alcohol dependency during exposure to negative emotional stimuli박미숙한국감성과학회 · 감성과학2018 · 제21권 제4호Altered Functional Connectivity of the Nucleus Accumbens and Amygdala in Cyber Addiction: A Resting State Functional Magnetic Resonance Imaging Study이문수, 이종하, Minsoo Ko, Sang-il Suh, Su-Hyuk Chi대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2023 · 제21권 제2호

이 간행물의 다른 논문 (17건)