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Cited by 24Neural and Behavioral Psychology StudiesSubstance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on Behavior

The prefrontal cortex as a critical gate of negative affect and motivation in alcohol use disorder

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Pahng, Amanda R, McGinn, M Adrienne, Paulsen, Rod I, Edwards, Scott·2017·Current Opinion in Behavioral Sciences
DOI 10.1016/j.cobeha.2016.11.004PMC PMC5242235
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Abstract

The prefrontal cortex (PFC) represents and executes the highest forms of goal-directed behavior, and has thereby attained a central neuroanatomical position in most pathophysiological conceptualizations of motivational disorders, including alcohol use disorder (AUD). Excessive, intermittent exposure to alcohol produces an allostatic dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis along with heightened forebrain glucocorticoid signaling that can damage PFC architecture and function. Negative affective states intimately associated with the transition to alcohol dependence result not only from a dysregulated HPA axis, but also from the inability of a damaged PFC to regulate subcortical stress and reinforcement centers, including the ventral striatum and amygdala. Several cognitive symptoms commonly associated with severe AUD, ranging from poor risk management to the cognitive/affective dimension of pain, are likely mediated by altered function of key anatomical elements that modulate PFC executive function, including contributions from the cingulate cortex and insula. Future therapeutic strategies for severe AUD should focus on attenuating the deleterious effects of excessive stress hormone activity on cognitive/affective and motivational behaviors gated by the PFC.

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  • Changes in neural circuitry caused by chronic stress are believed to underlie the deficits in learning/memory, mood, motivation, and reward seeking that are characteristic of depression and related disorders.

    “these changes in neural circuitry are believed to underlie the deficits in learning/memory, mood, motivation, and reward seeking that are characteristic of depression and related disorders (10, 67–74)”

    From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [71]

    The “Influence of Excessive Alcohol Exposure and Stress Hormones on Prefrontal Function” section (page unavailable) reports that chronic stress alters prefrontal structure and links stress-related prefrontal dysfunction to cognitive, affective, and motivational problems in alcohol use disorder. It does not establish that these changes underlie the stated deficits in depression and related disorders, or address reward seeking in that broader population. (LLM, conf=0.86)

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Research works printed but not linked: 42

  1. [3]Edwards S Baynes BB Carmichael CY Zamora-Martinez ER Barrus M Koob GF Gilpin NW Traumatic stress reactivity promotes excessive alcohol drinking and alters the balance of prefrontal cortex-amygdala activity Transl Psychiatry 2013 3 e296 23982628 PMC3756295
  2. [4]LeBlanc DM McGinn MA Itoga CA Edwards S The affective dimension of pain as a risk factor for drug and alcohol addiction Alcohol 2015 49 8 803 809 26008713 PMC4628900
  3. George O Koob GF Individual differences in prefrontal cortex function and the transition from drug use to drug dependence Neurosci Biobehav Rev 2010 35 2 232 247 A comprehensive and valuable review of prefrontal cortical areas and their afferent and efferent functional connections with respect to drug addiction-related symptomatology 20493211 PMC2955797
  4. Lu YL Richardson HN Alcohol, stress hormones, and the prefrontal cortex: A proposed pathway to the dark side of addiction Neuroscience 2014 277 139 151 Describes the manifestation and potentially harmful implications of neuroendocrine tolerance that occurs during the transition from alcohol use to dependence 24998895 PMC4164609
  5. [8]Edwards S Little HJ Richardson HN Vendruscolo LF Divergent regulation of distinct glucocorticoid systems in alcohol dependence Alcohol 2015 49 8 811 816 26003866 PMC4627854
  6. [9]Radley JJ Arias CM Sawchenko PE Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress J Neurosci 2006 26 50 12967 12976 17167086 PMC6674963
  7. [10]Wellman CL Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration J Neurobiol 2001 49 3 245 253 11745662
  8. [11]Radley JJ Rocher AB Rodriguez A Ehlenberger DB Dammann M McEwen BS Morrison JH Wearne SL Hof PR Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex J Comp Neurol 2008 507 1 1141 1150 18157834 PMC2796421
  9. [12]Tabakoff B Jafee RC Ritzmann RF Corticosterone concentrations in mice during ethanol drinking and withdrawal J Pharm Pharmacol 1978 30 6 371 374 26769
  10. [13]Adinoff B Martin PR Bone GH Eckardt MJ Roehrich L George DT Moss HB Eskay R Linnoila M Gold PW Hypothalamic-pituitary-adrenal axis functioning and cerebrospinal fluid corticotropin releasing hormone and corticotropin levels in alcoholics after recent and long-term abstinence Arch Gen Psychiatry 1990 47 4 325 330 2157379
  11. Little HJ Croft AP O’Callaghan MJ Brooks SP Wang G Shaw SG Selective increases in regional brain glucocorticoid: A novel effect of chronic alcohol Neuroscience 2008 156 4 1017 1027 Provided a novel neurobiological mechanism of alcohol-induced regulation of brain glucocorticoids relevant to cognition and AUD. Increased brain glucocorticoids were observed in both male and female mice and rats following chronic alcohol administration 18801418
  12. [15]Lee S Rivier C An initial, three-day-long treatment with alcohol induces a long-lasting phenomenon of selective tolerance in the activity of the rat hypothalamic-pituitary-adrenal axis J Neurosci 1997 17 22 8856 8866 9348353 PMC6573086
  13. [16]Richardson HN Chan SH Crawford EF Lee YK Funk CK Koob GF Mandyam CD Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence Neurobiol Dis 2009 36 1 1 10 19501165 PMC2742572
  14. [17]Vendruscolo LF Roberts AJ Operant alcohol self-administration in dependent rats: Focus on the vapor model Alcohol 2014 48 3 277 286 24290310 PMC4007394
  15. [18]Vendruscolo LF Barbier E Schlosburg JE Misra KK Whitfield TW Jr Logrip ML Rivier C Repunte-Canonigo V Zorrilla EP Sanna PP Heilig M Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats J Neurosci 2012 32 22 7563 7571 22649234 PMC3375621
  16. [20]Koenig HN Olive MF The glucocorticoid receptor antagonist mifepristone reduces ethanol intake in rats under limited access conditions Psychoneuroendocrinology 2004 29 8 999 1003 15219650
  17. Vendruscolo LF Estey D Goodell V Macshane LG Logrip ML Schlosburg JE McGinn MA Zamora-Martinez ER Belanoff JK Hunt HJ Sanna PP Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals J Clin Invest 2015 125 8 3193 3197 Translational evidence of mifepristone efficacy to reduce excessive drinking in both a preclinical model of severe alcohol use disorder and in alcohol-dependent human subjects 26121746 PMC4563748
  18. [22]Sullivan EV Pfefferbaum A Neurocircuitry in alcoholism: A substrate of disruption and repair Psychopharmacology (Berl) 2005 180 4 583 594 15834536
  19. Holmes A Fitzgerald PJ MacPherson KP DeBrouse L Colacicco G Flynn SM Masneuf S Pleil KE Li C Marcinkiewcz CA Kash TL Chronic alcohol remodels prefrontal neurons and disrupts nmdar-mediated fear extinction encoding Nat Neurosci 2012 15 10 1359 1361 Demonstrates the drastic consequences of chronic alcohol exposure on prefrontal function and the development of trauma-related anxiety 22941108 PMC3471649
  20. [24]Kroener S Mulholland PJ New NN Gass JT Becker HC Chandler LJ Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex PLoS One 2012 7 5 e37541 22666364 PMC3364267
  21. [25]Errico AL King AC Lovallo WR Parsons OA Cortisol dysregulation and cognitive impairment in abstinent male alcoholics Alcohol Clin Exp Res 2002 26 8 1198 1204 12198394
  22. [26]Rose AK Shaw SG Prendergast MA Little HJ The importance of glucocorticoids in alcohol dependence and neurotoxicity Alcohol Clin Exp Res 2010 34 12 2011 2018 21087289 PMC3058879
  23. [27]George O Sanders C Freiling J Grigoryan E Vu S Allen CD Crawford E Mandyam CD Koob GF Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking Proc Natl Acad Sci U S A 2012 109 44 18156 18161 23071333 PMC3497825
  24. [28]Jacquot C Croft AP Prendergast MA Mulholland P Shaw SG Little HJ Effects of the glucocorticoid antagonist, mifepristone, on the consequences of withdrawal from long term alcohol consumption Alcohol Clin Exp Res 2008 32 12 2107 2116 18828802
  25. [29]Baumeister RF Ego depletion and self-regulation failure: A resource model of self-control Alcohol Clin Exp Res 2003 27 2 281 284 12605077
  26. Seif T Chang SJ Simms JA Gibb SL Dadgar J Chen BT Harvey BK Ron D Messing RO Bonci A Hopf FW Cortical activation of accumbens hyperpolarization-active nmdars mediates aversion-resistant alcohol intake Nat Neurosci 2013 16 8 1094 1100 Optogenetic interrogation of the prefrontal circuitry responsible for drinking in the face of adverse consequences 23817545 PMC3939030
  27. [33]Riley JL King C Self-report of alcohol use for pain in a multi-ethnic community sample Journal of Pain 2009 204 423 429 PMC2734914 19712901
  28. [34]Edwards S Vendruscolo LF Schlosburg JE Misra KK Wee S Park PE Schulteis G Koob GF Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: Alleviation by crf(1) receptor antagonism Neuropharmacology 2012 62 2 1142 1151 22119954 PMC3262951
  29. [37]Vogt BA Pain and emotion interactions in subregions of the cingulate gyrus Nat Rev Neurosci 2005 6 7 533 544 15995724 PMC2659949
  30. [38]Ploghaus A Tracey I Gati JS Clare S Menon RS Matthews PM Rawlins JN Dissociating pain from its anticipation in the human brain Science 1999 2845422 1979 1981 10373114
  31. [39]Casey KL Concepts of pain mechanisms: The contribution of functional imaging of the human brain Prog Brain Res 2000 129 277 287 11098696
  32. [40]Fuchs PN Peng YB Boyette-Davis JA Uhelski ML The anterior cingulate cortex and pain processing Front Integr Neurosci 2014 8 35 24829554 PMC4017137
  33. [41]Menon V Uddin LQ Saliency, switching, attention and control: A network model of insula function Brain Struct Funct 2010 214 5–6 655 667 20512370 PMC2899886
  34. [42]Zhu X Sundby K Bjork JM Momenan R Alcohol dependence and altered engagement of brain networks in risky decisions Front Hum Neurosci 2016 10 142 27064561 PMC4814760
  35. [43]Seo D Lacadie CM Sinha R Neural correlates and connectivity underlying stress-related impulse control difficulties in alcoholism Alcohol Clin Exp Res 2016 40 9 1884 1894 27501356 PMC5008995
  36. [44]Donoghue K Rose A Coulton S Milward J Reed K Drummond C Little H Double-blind, 12 month follow-up, placebo-controlled trial of mifepristone on cognition in alcoholics: The mifcog trial protocol BMC Psychiatry 2016 16 40 26912003 PMC4765152
  37. [45]Costin BN Wolen AR Fitting S Shelton KL Miles MF Role of adrenal glucocorticoid signaling in prefrontal cortex gene expression and acute behavioral responses to ethanol Alcohol Clin Exp Res 2013 37 1 57 66 22671426 PMC3507324
  38. [46]Fernandez GM Stewart WN Savage LM Chronic drinking during adolescence predisposes the adult rat for continued heavy drinking: Neurotrophin and behavioral adaptation after long-term, continuous ethanol exposure PLoS One 2016 11 3 e0149987 26930631 PMC4773001
  39. [47]Crews FT Vetreno RP Neuroimmune basis of alcoholic brain damage Int Rev Neurobiol 2014 118 315 357 25175868 PMC5765863
  40. [48]Barbier E Johnstone AL Khomtchouk BB Tapocik JD Pitcairn C Rehman F Augier E Borich A Schank JR Rienas CA Van Booven DJ Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase prdm2 Mol Psychiatry 2016 PMC5677579 27573876
  41. Retson TA Sterling RC Van Bockstaele EJ Alcohol-induced dysregulation of stress-related circuitry: The search for novel targets and implications for interventions across the sexes Prog Neuropsychopharmacol Biol Psychiatry 2016 65 252 259 This review sets the stage for future investigations into sex as a highly relevant variable at the intersection of stress and AUD treatment 26006055 PMC4656147
  42. [50]Wilhelm CJ Hashimoto JG Roberts ML Bloom SH Beard DK Wiren KM Females uniquely vulnerable to alcohol-induced neurotoxicity show altered glucocorticoid signaling Brain Res 2015 1601 102 116 25601008 PMC4362524

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Authors
Pahng, A. R., McGinn, M. A., Paulsen, R. I., & Edwards, S.
Affiliations
Louisiana State University Health Sciences Center New Orleans (US)
Corresponding author
Edwards, Scott
ORCID
Venue
Current Opinion in Behavioral Sciences
Publisher
Elsevier BV
Published
2017-02
Volume
13
Pages
139-143
ISSN
2352-1546 (ISSN-L)
DOI
10.1016/j.cobeha.2016.11.004
PMC
PMC5242235
OpenAlex
W2565197760
Cited by
24
References
8
Citations by year
2026: 3 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 4
FWCI
0.25
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Current Opinion in Behavioral Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • LSUHSC-New Orleans Comprehensive Alcohol-HIV/AIDS Research Center
  • National Institute on Alcohol Abuse and Alcoholism
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
prefrontal cortex, alcoholism, negative affect, motivation, HPA axis dysregulation, glucocorticoid signaling, ventral striatum, amygdala, executive function, cingulate cortex, insula, stress hormones, cognitive symptoms

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