Skip to main content
SpringerLink
Log in

Anhedonia, Hyperkatifeia, and Negative Reinforcement in Substance Use Disorders

  • Chapter
  • First Online:
Anhedonia: Preclinical, Translational, and Clinical Integration

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 58))

Abstract

Drug addiction has been defined as a chronically relapsing disorder that is characterized by a compulsion to seek and take a drug or stimulus, the loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug or stimulus is prevented, a component of which is anhedonia. The present review explores a heuristic framework for understanding the role of anhedonia in addiction, in which anhedonia is a key component of hyperkatifeia (conceptualized as the potentiated intensity of negative emotional/motivational symptoms during drug withdrawal) and negative reinforcement in addiction. The neural substrates that mediate such anhedonia and crosstalk between elements of hyperkatifeia that contribute to anhedonia are then explored, including crosstalk between physical pain and emotional pain systems. The present review explores current knowledge of neurochemical neurocircuitry changes that are associated with conditioned hyperkatifeia/anhedonia. The overall hypothesis is that the shift in motivation toward negative reinforcement in addiction reflects the allostatic misregulation of hedonic tone, such that drug taking makes anhedonia worse during the process of seeking temporary relief by compulsive drug taking, thereby perpetuating the addiction cycle and hedonic comorbidities that are associated with addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ahmed SH, Koob GF (2005) The transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function. Psychopharmacology 180:473–490

    Article  CAS  PubMed  Google Scholar 

  • Alheid GF, De Olmos JS, Beltramino CA (1995) Amygdala and extended amygdala. In: Paxinos G (ed) The rat nervous system, 2nd edn. Academic Press, San Diego, pp 495–578

    Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, Washington

    Book  Google Scholar 

  • Ashok AH, Mizuno Y, Volkow ND et al (2017) Association of stimulant use with dopaminergic alterations in users of cocaine, amphetamine, or methamphetamine: a systematic review and meta-analysis. JAMA Psychiatry 74:511–519

    Article  PubMed  PubMed Central  Google Scholar 

  • Baker TB, Morse E, Sherman JE (1987) The motivation to use drugs: a psychobiological analysis of urges. In: River PC (ed) Alcohol and addictive behavior, Nebraska symposium on motivation, vol vol 34. University of Nebraska Press, Lincoln, pp 257–323

    Google Scholar 

  • Baker TB, Piper ME, McCarthy DE et al (2004) Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev 111:33–51

    Article  PubMed  Google Scholar 

  • Bentzley BS, Barth KS, Back SE et al (2015) Patient perspectives associated with intended duration of buprenorphine maintenance therapy. J Subst Abus Treat 56:48–53

    Article  Google Scholar 

  • Bester H, Menendez L, Besson JM et al (1995) Spino (trigemino) parabrachiohypothalamic pathway: electrophysiological evidence for an involvement in pain processes. J Neurophysiol 73:568–585

    Article  CAS  PubMed  Google Scholar 

  • Bogdan R, Santesso DL, Fagerness J et al (2011) Corticotropin-releasing hormone receptor type 1 (CRHR1) genetic variation and stress interact to influence reward learning. J Neurosci 31:13246–13254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breiter HC, Gollub RL, Weisskoff RM et al (1997) Acute effects of cocaine on human brain activity and emotion. Neuron 19:591–611

    Article  CAS  PubMed  Google Scholar 

  • Bryce CA, Floresco SB (2016) Perturbations in effort-related decision-making driven by acute stress and corticotropin-releasing factor. Neuropsychopharmacology 41:2147–2159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carlezon WA Jr, Nestler EJ, Neve RL (2000) Herpes simplex virus-mediated gene transfer as a tool for neuropsychiatric research. Crit Rev Neurobiol 14:47–67

    Article  CAS  PubMed  Google Scholar 

  • Carmack SA, Keeley RJ, Vendruscolo JCM et al (2019) Heroin addiction engages negative emotional learning brain circuits in rats. J Clin Invest 130:2480–2484

    Article  Google Scholar 

  • Case A, Deaton A (2015) Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. Proc Natl Acad Sci U S A 112:15078–15083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chapman LJ, Chapman JP, Raulin ML (1976) Scales for physical and social anhedonia. J Abnorm Psychol 85:374–382

    Article  CAS  PubMed  Google Scholar 

  • Chen AC, Manz N, Tang Y et al (2010) Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. Alcohol Clin Exp Res 34:988–996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colpaert FC (1996) System theory of pain and of opiate analgesia: no tolerance to opiates. Pharmacol Rev 48:355–402

    CAS  PubMed  Google Scholar 

  • de Jong JW, Afjei SA, Pollak Dorocic I et al (2019) A neural circuit mechanism for encoding aversive stimuli in the mesolimbic dopamine system. Neuron 101:133–151.e7

    Article  PubMed  CAS  Google Scholar 

  • Delfs JM, Zhu Y, Druhan JP et al (2000) Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature 403:430–434

    Article  CAS  PubMed  Google Scholar 

  • Dina OA, Barletta J, Chen X et al (2000) Key role for the epsilon isoform of protein kinase C in painful alcoholic neuropathy in the rat. J Neurosci 20:8614–8619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dina OA, Messing RO, Levine JD (2006) Ethanol withdrawal induces hyperalgesia mediated by PKCε. Eur J Neurosci 24:197–204

    Article  PubMed  Google Scholar 

  • Dolinsky ZS, Morse DE, Kaplan RF et al (1987) Neuroendocrine, psychophysiological and subjective reactivity to an alcohol placebo in male alcoholic patients. Alcohol Clin Exp Res 11:296–300

    Article  CAS  PubMed  Google Scholar 

  • Doverty M, White JM, Somogyi AA et al (2001) Hyperalgesic responses in methadone maintenance patients. Pain 90:91–96

    Article  CAS  PubMed  Google Scholar 

  • Drummond CD, Cooper T, Glautier SP (1990) Conditioned learning in alcohol dependence: implications for cue exposure treatment. Br J Addict 85:725–743

    Article  CAS  PubMed  Google Scholar 

  • Edwards S, Vendruscolo LF, Schlosburg JE et al (2012) Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: alleviation by CRF1 receptor antagonism. Neuropharmacology 62:1142–1151

    Article  CAS  PubMed  Google Scholar 

  • Evans CJ, Cahill CM (2016) Neurobiology of opioid dependence in creating addiction vulnerability. F1000Res 5:F1000 Faculty Rev-1748

    Article  PubMed  PubMed Central  Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489. Erratum in: Nat Neurosci 9:979

    Article  CAS  PubMed  Google Scholar 

  • Fu Y, Neugebauer V (2008) Differential mechanisms of CRF1 and CRF2 receptor functions in the amygdala in pain-related synaptic facilitation and behavior. J Neurosci 28:3861–3876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gauriau C, Bernard JF (2004) Posterior triangular thalamic neurons convey nociceptive messages to the secondary somatosensory and insular cortices in the rat. J Neurosci 24:752–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gawin FH, Kleber HD (1986) Abstinence symptomatology and psychiatric diagnosis in cocaine abusers: clinical observations. Arch Gen Psychiatry 43:107–113

    Article  CAS  PubMed  Google Scholar 

  • Goldberg SR, Woods JH, Schuster CR (1969) Morphine: conditioned increases in self-administration in rhesus monkeys. Science 166:1306–1307

    Article  CAS  PubMed  Google Scholar 

  • Gracy KN, Dankiewicz LA, Koob GF (2001) Opiate withdrawal-induced Fos immunoreactivity in the rat extended amygdala parallels the development of conditioned place aversion. Neuropsychopharmacology 24:152–160

    Article  CAS  PubMed  Google Scholar 

  • Grieder TE, Herman MA, Contet C et al (2014) VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation. Nat Neurosci 17:1751–1758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haber SN, Fudge JL, McFarland NR (2000) Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci 20:2369–2382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Handelsman L, Aronson MJ, Ness R et al (1992) The dysphoria of heroin addiction. Am J Drug Alcohol Abuse 18:275–287

    Article  CAS  PubMed  Google Scholar 

  • Heimer L, Alheid G (1991) Piecing together the puzzle of basal forebrain anatomy. In: Napier TC, Kalivas PW, Hanin I (eds) The basal forebrain: anatomy to function, Advances in experimental medicine and biology, vol vol 295. Plenum Press, New York, pp 1–42

    Chapter  Google Scholar 

  • Heinrichs SC, Menzaghi F, Schulteis G et al (1995) Suppression of corticotropin-releasing factor in the amygdala attenuates aversive consequences of morphine withdrawal. Behav Pharmacol 6:74–80

    Article  CAS  PubMed  Google Scholar 

  • Himmelsbach CK (1943) Can the euphoric, analgetic, and physical dependence effects of drugs be separated? IV. With reference to physical dependence. Fed Proc 2:201–203

    CAS  Google Scholar 

  • Ho A, Dole VP (1979) Pain perception in drug-free and in methadone-maintained human ex-addicts. Proc Soc Exp Biol Med 162:392–395

    Article  CAS  PubMed  Google Scholar 

  • Hummel M, Cummons T, Lu P et al (2010) Pain is a salient “stressor” that is mediated by corticotropin-releasing factor-1 receptors. Neuropharmacology 59:160–166

    Article  CAS  PubMed  Google Scholar 

  • Ji G, Fu Y, Ruppert KA et al (2007) Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala. Mol Pain 3:13

    PubMed  PubMed Central  Google Scholar 

  • Jochum T, Boettger MK, Burkhardt C et al (2010) Increased pain sensitivity in alcohol withdrawal syndrome. Eur J Pain 14:713–718

    Article  CAS  PubMed  Google Scholar 

  • Kanof PD, Handelsman L, Aronson MJ et al (1992) Clinical characteristics of naloxone-precipitated withdrawal in human opioid-dependent subjects. J Pharmacol Exp Ther 260:355–363

    CAS  PubMed  Google Scholar 

  • Kelsey JE, Verhaak AM, Schierberl KC (2015) The kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), decreases morphine withdrawal and the consequent conditioned place aversion in rats. Behav Brain Res 283:16–21

    Article  CAS  PubMed  Google Scholar 

  • Kenny PJ, Gasparini F, Markou A (2003) Group II metabotropic and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate glutamate receptors regulate the deficit in brain reward function associated with nicotine withdrawal in rats. J Pharmacol Exp Ther 306:1068–1076

    Article  CAS  PubMed  Google Scholar 

  • Kenny PJ, Chen SA, Kitamura O et al (2006) Conditioned withdrawal drives heroin consumption and decreases reward sensitivity. J Neurosci 26:5894–5900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koob GF (2008) A role for brain stress systems in addiction. Neuron 59:11–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koob GF (2015) The dark side of emotion: the addiction perspective. Eur J Pharmacol 753:73–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koob GF (2017) Antireward, compulsivity, and addiction: seminal contributions of Dr. Athina Markou to motivational dysregulation in addiction. Psychopharmacology 234:1315–1332

    Article  CAS  PubMed  Google Scholar 

  • Koob GF (2020) Neurobiology of opioid addiction: opponent process, hyperkatifeia and negative reinforcement. Biol Psychiatry 87:44–53

    Article  CAS  PubMed  Google Scholar 

  • Koob GF (2021) Drug addiction: hyperkatifeia/negative reinforcement as a framework for medications development. Pharmacol Rev 73:163–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2008) Addiction and the brain antireward system. Annu Rev Psychol 59:29–53

    Article  PubMed  Google Scholar 

  • Koob GF, Schulkin J (2019) Addiction and stress: an allostatic view. Neurosci Biobehav Rev 106:245–262

    Article  PubMed  Google Scholar 

  • Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacol Rev 35:217–238. Erratum 35:1051

    Article  Google Scholar 

  • Koob GF, Volkow ND (2016) Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry 3:760–773

    Article  PubMed  PubMed Central  Google Scholar 

  • Koob GF, Powell P, White A (2020) Addiction as a coping response: hyperkatifeia, deaths of despair, and COVID-19. Am J Psychiatry 177:1031–1037

    Article  PubMed  Google Scholar 

  • Krystal AD, Pizzagalli DA, Smoski M et al (2020) A randomized proof-of-mechanism trial applying the ‘fast-fail’ approach to evaluating κ-opioid antagonism as a treatment for anhedonia. Nat Med 26:760–768

    Article  CAS  PubMed  Google Scholar 

  • Kwako LE, Schwandt ML, Ramchandani VA et al (2019) Neurofunctional domains derived from deep behavioral phenotyping in alcohol use disorder. Am J Psychiatry 176:744–753

    Article  PubMed  PubMed Central  Google Scholar 

  • Lal H, Miksic S, Drawbaugh R et al (1976) Alleviation of narcotic withdrawal syndrome by conditional stimuli. Pavlov J Biol Sci 11:251–262

    Article  CAS  PubMed  Google Scholar 

  • Laulin JP, Celerier E, Larcher A et al (1999) Opiate tolerance to daily heroin administration: an apparent phenomenon associated with enhanced pain sensitivity. Neuroscience 89:631–636

    Article  CAS  PubMed  Google Scholar 

  • Lemos JC, Wanat MJ, Smith JS et al (2012) Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive. Nature 490:402–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Schulteis G (2004) Brain reward deficits accompany naloxone-precipitated withdrawal from acute opioid dependence. Pharmacol Biochem Behav 79:101–108

    Article  CAS  PubMed  Google Scholar 

  • Lowman C, Allen J, Stout RL (1996) Replication and extension of Marlatt’s taxonomy of relapse precipitants: overview of procedures and results. Addiction 91(suppl):s51–s71

    Article  PubMed  Google Scholar 

  • Lucas M, Frenois F, Vouillac C et al (2008) Reactivity and plasticity in the amygdala nuclei during opiate withdrawal conditioning: differential expression of c-fos and arc immediate early genes. Neuroscience 154:1021–1033

    Article  CAS  PubMed  Google Scholar 

  • Ludwig EM (1975) The irresistable urge and the unquenchable thirst for alcohol. In: Chafetz ME (ed) Proceedings of the fourth annual alcoholism conference of the National Institute on Alcohol Abuse and Alcoholism: research, treatment and prevention, Washington, D.C, June 12–14, 1974. National Institute on Alcohol Abuse and Alcoholism, Rockville, pp 3–22

    Google Scholar 

  • Lynch JJ, Fertziger AP, Teitelbaum HA et al (1973) Pavlovian conditioning of drug reactions: some implications for problems of drug addiction. Cond Reflex 8:211–223

    Article  CAS  PubMed  Google Scholar 

  • Marchette RCN, Gregory-Flores A, Tunstall BJ et al (2021) κ-Opioid receptor antagonism reverses heroin withdrawal-induced hyperalgesia in male and female rats. Neurobiol Stress 14:100325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marlatt GA (1969) Taxonomy of high-risk situations for alcohol relapse: evolution and development of a cognitive-behavioral model. Addiction 91(suppl):S37–S49

    Google Scholar 

  • Marlatt GA (1985) Relapse prevention: introduction and overview of the model. In: Marlatt GA, Gordon JR (eds) Relapse prevention: maintenance strategies in the treatment of addictive behaviors. Guilford, London, pp 3–70

    Google Scholar 

  • Marlatt G, Gordon J (1980) Determinants of relapse: implications for the maintenance of behavioral change. In: Davidson P, Davidson S (eds) Behavioral medicine: changing health lifestyles. Brunner/Mazel, New York, pp 410–452

    Google Scholar 

  • Martin WR (1968) A homeostatic and redundancy theory of tolerance to and dependence on narcotic analgesics. In: Wikler A (ed) The addictive states, Its research publications, vol vol 46. Williams and Wilkins, Baltimore, pp 206–225

    Google Scholar 

  • Massaly N, Copits BA, Wilson-Poe AR et al (2019) Pain-induced negative affect is mediated via recruitment of the nucleus accumbens kappa opioid system. Neuron 102:564–573.e6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McNally GP, Akil H (2002) Role of corticotropin-releasing hormone in the amygdala and bed nucleus of the stria terminalis in the behavioral, pain modulatory, and endocrine consequences of opiate withdrawal. Neuroscience 112:605–617

    Article  CAS  PubMed  Google Scholar 

  • Meyer RE, Mirin SM (1979) The heroin stimulus: implications for a theory of addiction. Plenum, New York

    Book  Google Scholar 

  • Nestler EJ (2004) Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol Sci 25:210–218

    Article  CAS  PubMed  Google Scholar 

  • Neugebauer V (2007) The amygdala: different pains, different mechanisms. Pain 127:1–2

    Article  PubMed  Google Scholar 

  • Neugebauer V, Li W (2002) Processing of nociceptive mechanical and thermal information in central amygdala neurons with knee-joint input. J Neurophysiol 87:103–112

    Article  PubMed  Google Scholar 

  • O’Brien CP (1974) “Needle freaks”: psychological dependence on shooting up. Medical World News, Psychiatry Annual

    Google Scholar 

  • O’Brien CP, Testa T, O’Brien TJ et al (1977) Conditioned narcotic withdrawal in humans. Science 195:1000–1002

    Article  PubMed  Google Scholar 

  • Pantazis CB, Gonzalez LA, Tunstall BJ et al (2021) Cues conditioned to withdrawal and negative reinforcement: neglected but key motivational elements driving opioid addiction. Sci Adv 7:eabf0364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park PE, Schlosburg JE, Vendruscolo LF et al (2015) Chronic CRF1 receptor blockade reduces heroin intake escalation and dependence-induced hyperalgesia. Addict Biol 20:275–284

    Article  CAS  PubMed  Google Scholar 

  • Pecina S, Schulkin J, Berridge KC (2006) Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress? BMC Biol 4:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pergolizzi JV Jr, Raffa RB, Rosenblatt MH (2020) Opioid withdrawal symptoms, a consequence of chronic opioid use and opioid use disorder: current understanding and approaches to management. J Clin Pharm Ther 45:892–903

    Article  PubMed  Google Scholar 

  • Price DD (2000) Psychological and neural mechanisms of the affective dimension of pain. Science 288:1769–1772

    Article  CAS  PubMed  Google Scholar 

  • Schulteis G, Liu J (2006) Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats. Alcohol 39:21–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulteis G, Markou A, Gold LH et al (1994) Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis. J Pharmacol Exp Ther 271:1391–1398

    CAS  PubMed  Google Scholar 

  • Schulteis G, Ahmed SH, Morse AC et al (2000) Conditioning and opiate withdrawal: the amygdala links neutral stimuli with the agony of overcoming drug addiction. Nature 405:1013–1014

    Article  CAS  PubMed  Google Scholar 

  • Shanahan L, Hill SN, Gaydosh LM et al (2019) Does despair really kill? A roadmap for an evidence-based answer. Am J Public Health 109:854–858

    Article  PubMed  PubMed Central  Google Scholar 

  • Shippenberg TS, Zapata A, Chefer VI (2007) Dynorphin and the pathophysiology of drug addiction. Pharmacol Ther 116:306–321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shurman J, Koob GF, Gutstein HB (2010) Opioids, pain, the brain, and hyperkatifeia: a framework for the rational use of opioids for pain. Pain Med 11:1092–1098

    Article  PubMed  Google Scholar 

  • Simpson S, Kimbrough A, Boomhower B et al (2020) Depletion of the microbiome alters the recruitment of neuronal ensembles of oxycodone intoxication and withdrawal. eNeuro 7:ENEURO.0312-19.2020

    Article  PubMed  PubMed Central  Google Scholar 

  • Solomon RL (1980) The opponent-process theory of acquired motivation: the costs of pleasure and the benefits of pain. Am Psychol 35:691–712

    Article  CAS  PubMed  Google Scholar 

  • Solomon RL, Corbit JD (1973) An opponent-process theory of motivation: II. Cigarette addiction. J Abnorm Psychol 81:158–171

    Article  CAS  PubMed  Google Scholar 

  • Solomon RL, Corbit JD (1974) An opponent-process theory of motivation: 1. Temporal dynamics of affect. Psychol Rev 81:119–145

    Article  CAS  PubMed  Google Scholar 

  • Stanton CH, Holmes AJ, Chang SWC et al (2019) From stress to anhedonia: molecular processes through functional circuits. Trends Neurosci 42:23–42

    Article  CAS  PubMed  Google Scholar 

  • Thomsen KR (2015) Measuring anhedonia: impaired ability to pursue, experience, and learn about reward. Front Psychol 6:1409

    Article  PubMed  PubMed Central  Google Scholar 

  • Todtenkopf MS, Marcus JF, Portoghese PS et al (2004) Effects of κ-opioid receptor ligands on intracranial self-stimulation in rats. Psychopharmacology 172:463–470

    Article  CAS  PubMed  Google Scholar 

  • Treutlein J, Kissling C, Frank J et al (2006) Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples. Mol Psychiatry 11:594–602

    Article  CAS  PubMed  Google Scholar 

  • Tsai PJ, Keeley RJ, Carmack SA et al (2020) Converging structural and functional evidence for a rat salience network. Biol Psychiatry 88:867–878

    Article  CAS  PubMed  Google Scholar 

  • Voon V, Grodin E, Mandali A et al (2020) Addictions NeuroImaging assessment (ANIA): towards an integrative framework for alcohol use disorder. Neurosci Biobehav Rev 113:492–506

    Article  PubMed  Google Scholar 

  • Walsh JJ, Friedman AK, Sun H et al (2014) Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway. Nat Neurosci 17:27–29

    Article  CAS  PubMed  Google Scholar 

  • Wanat MJ, Hopf FW, Stuber GD et al (2008) Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih. J Physiol 586:2157–2170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wanat MJ, Bonci A, Phillips PE (2013) CRF acts in the midbrain to attenuate accumbens dopamine release to rewards but not their predictors. Nat Neurosci 16:383–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss RD, Potter JS, Griffin ML et al (2014) Reasons for opioid use among patients with dependence on prescription opioids: the role of chronic pain. J Subst Abus Treat 47:140–145

    Article  Google Scholar 

  • Whitton AE, Treadway MT, Pizzagalli DA (2015) Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry 28:7–12

    Article  PubMed  PubMed Central  Google Scholar 

  • Wikler A (1973) Dynamics of drug dependence: implications of a conditioning theory for research and treatment. Arch Gen Psychiatry 28:611–616

    Article  CAS  PubMed  Google Scholar 

  • Woolf SH, Schoomaker H (2019) Life expectancy and mortality rates in the United States, 1959-2017. JAMA 322:1996–2016

    Article  PubMed  PubMed Central  Google Scholar 

  • Xi ZX, Fuller SA, Stein EA (1998) Dopamine release in the nucleus accumbens during heroin self-administration is modulated by kappa opioid receptors: an in vivo fast-cyclic voltammetry study. J Pharmacol Exp Ther 284:151–161

    CAS  PubMed  Google Scholar 

  • Zywiak WH, Connors GJ, Maisto SA et al (1996) Relapse research and the reasons for drinking questionnaire: a factor analysis of Marlatt’s relapse taxonomy. Addiction 91(suppl):s121–s130

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The author thanks Michael Arends for assistance with manuscript preparation.

Author information

Authors and Affiliations

  1. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA

    George F. Koob

  2. National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA

    George F. Koob

Authors
  1. George F. Koob
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George F. Koob .

Editor information

Editors and Affiliations

  1. Harvard Medical School and McLean Hospital, Belmont, MA, USA

    Diego A. Pizzagalli

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Koob, G.F. (2022). Anhedonia, Hyperkatifeia, and Negative Reinforcement in Substance Use Disorders. In: Pizzagalli, D.A. (eds) Anhedonia: Preclinical, Translational, and Clinical Integration. Current Topics in Behavioral Neurosciences, vol 58. Springer, Cham. https://doi.org/10.1007/7854_2021_288

Download citation

Publish with us

Policies and ethics

Search

Navigation