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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]
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“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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“Figure 7 shows that TNFα increased firing rates and facilitated GABA release in the CeA, an area of the brain long known to regulate emotional behavior and ethanol withdrawal behaviors (Knapp et al., 2007; Koob, 2009).”
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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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