The DOI matches its Crossref record; 111 of the 112 references it cites were found in a registry or an index.
Brain stress systems in the amygdala and addiction
Open accessAbstract
Dysregulation of the brain emotional systems that mediate arousal and stress is a key component of the pathophysiology of drug addiction. Drug addiction is a chronically relapsing disorder characterized by a compulsion to seek and take drugs and the development of dependence and manifestation of a negative emotional state when the drug is removed. Activation of brain stress systems is hypothesized to be a key element of the negative emotional state produced by dependence that drives drug-seeking through negative reinforcement mechanisms. The focus of the present review is on the role of two key brain arousal/stress systems in the development of dependence. Emphasis is placed on the neuropharmacological actions of corticotropin-releasing factor (CRF) and norepinephrine in extrahypothalamic systems in the extended amygdala, including the central nucleus of the amygdala, bed nucleus of the stria terminalis, and a transition area in the shell of the nucleus accumbens. Compelling evidence argues that these brain stress systems, a heretofore largely neglected component of dependence and addiction, play a key role in engaging the transition to dependence and maintaining dependence once it is initiated. Understanding the role of the brain stress and anti-stress systems in addiction not only provides insight into the neurobiology of the "dark side" of addiction but also provides insight into the organization and function of basic brain emotional circuitry that guides motivated behavior.
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“The distress and negative emotions of withdrawal are associated on the one hand with reduced dopamine signaling in response to rewards (anhedonia) and on the other with an enhanced sensitiv ity of the brain's stress system, including the extended amygdala, habenula and hypothalamus 66 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [66]
Experimental — accuracy not yet measuredIn the citing paper
“Recruitment of brain stress amygdale activation has been suggested to cause the negative motivational state that drives addicitoin (Koob, 2009).”
From Impulsivity, frontal lobes and risk for addiction (2009) · cites this paper as Koob, 2009
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Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
A Syndrome produced by Diverse Nocuous Agents
Selye, H. (1936) · Nature · doi:10.1038/138032a0 · Cited by 3,967
Drug Addiction, Dysregulation of Reward, and Allostasis
Koob, G. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00195-0 · Cited by 2,953
Self-citationDrug abuse: hedonic homeostatic dysregulation
Koob, G. F., & Moal, M. L. (1997) · Science · doi:10.1126/science.278.5335.52 · Cited by 2,535
Self-citationSwanson, L. W., Sawchenko, P. E., Rivier, J., & Vale, W. W. (2008) · Neuroendocrinology · doi:10.1159/000123454 · Cited by 1,953
The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress
Smith, S. M., & Vale, W. W. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.4/ssmith · Cited by 1,948
The reinstatement model of drug relapse: history, methodology and major findings
Shaham, Y., Shalev, U., Lu, L., de Wit, H., & Stewart, J. (2003) · Psychopharmacology · doi:10.1007/s00213-002-1224-x · Cited by 1,615
Addiction and the brain antireward system
Koob, G. F., & Le Moal, M. (2008) · Annual Review of Psychology · doi:10.1146/annurev.psych.59.103006.093548 · Cited by 1,457
Self-citationAllostasis: A New Paradigm to Explain Arousal Pathology
Sterling, P., & Eyer, J. (1988) · Zenodo · doi:10.5281/zenodo.13537700 · Cited by 1,450
Handbook of Life Stress, Cognition and Health
PASTOR, L. H. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.10.1347 · Cited by 1,402
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Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340
Self-citationRethinking the Emotional Brain
LeDoux, J. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.004 · Cited by 1,594
“…1980; Balleine and Killcross, 1994; Killcross and Robbins, 1993; Everitt et al., 1999; Cardinal et al., 2002; Ikemoto and Panksepp, 1999; Parkinson et al., 1999; Koob, 2009; Sesack and Grace, 2010; Berridge, 2007, 2009; Berridge and Robinson, 1998; Hyman et al., 2006; Nestler, 2004; Kelley, 2004).”
Amygdala circuitry mediating reversible and bidirectional control of anxiety
Tye, K. M., Prakash, R., Kim, S.-Y., Fenno, L. E., Grosenick, L., Zarabi, H., Thompson, K. R., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K. (2011) · Nature · doi:10.1038/nature09820 · Cited by 1,289
Stress-induced obesity and the emotional nervous system
Dallman, M. F. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.10.004 · Cited by 814
Impulsivity, frontal lobes and risk for addiction
Crews, F. T., & Boettiger, C. A. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.04.018 · Cited by 679
“Impulsive choice is one aspect of impulsivity that involves the choice of small, sooner rewards over larger, delayed rewards (Cardinal et al., 2004).”
Background
Metadata
- Authors
- Koob, G. F.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Koob, George F.
- ORCID
- Koob, George F.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 1293
- Pages
- 61-75
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2774745
- OpenAlex
- W2010555262
- Cited by
- 388
- References
- 112
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 22 · 2023: 17 · 2022: 20 · 2021: 24 · 2020: 31 · 2019: 33 · 2018: 34 · 2017: 20 · 2016: 25 · 2015: 28 · 2014: 24 · 2013: 24 · 2012: 20
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA008459, AA-06420, AA-08459, P50AA006420, R37AA008459, P60AA006420)
- National Institute on Drug Abuse (DA04043, DA04398, R01DA004398, R01DA004043)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- drug addiction, extended amygdala, corticotropin-releasing factor, norepinephrine, central amygdala, bed nucleus of the stria terminalis, nucleus accumbens shell, negative reinforcement, emotional arousal, relapse, motivated behavior
- MeSH terms
- Amygdala, Animals, Compulsive Behavior, Corticotropin-Releasing Hormone, Humans, Hypothalamo-Hypophyseal System, Motivation, Norepinephrine, Pituitary-Adrenal System, Stress, Psychological, Substance Withdrawal Syndrome, Substance-Related Disorders
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