The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Drug Addiction, Dysregulation of Reward, and Allostasis
Abstract
This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drug-taking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop…
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“Though valuation processes are fundamental to survival of the human species, hedonic dysregulation is at the root of an array of clinical disorders, including addiction, stress, and chronic pain, as evidenced by the allostatic shift in the relative salience of natural reward to drug reward observed among persons with severe substance use disorders.”
In the citing paper
“The emergence of negative affective symptoms, such as dysphoria, anxiety and irritability and, to a lesser extent, the somatic manifestations of withdrawal, serve as negative reinforcers that sustain the vicious cycle of addiction [23, 121, 132–134].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [132]
In the citing paper
“but reward insensitivity and negative reinforcement underlie the later and more severe stages(18–20).”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [18]
In the citing paper
“Finally, allostatic theory asserts heightened brain reward sensitivity and positive reinforcement characterize the early stages of addiction(18), but reward insensitivity and negative reinforcement underlie the later and more severe stages(18–20).”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [18]
In the citing paper
“Limitations included that the reexamination interval may not have been sufficient to observe the extent of neuroadaptative responses to alcohol(18)”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [18]
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Metadata
- Authors
- Koob, G.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Koob, G
- Venue
- Neuropsychopharmacology
- Published
- 2001-02
- Volume
- 24
- Issue
- 2
- Pages
- 97-129
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W1989416066
- Cited by
- 2,953
- References
- 37
- Citations by year
- 2026: 72 · 2025: 94 · 2024: 73 · 2023: 105 · 2022: 85 · 2021: 136 · 2020: 162 · 2019: 124 · 2018: 118 · 2017: 139 · 2016: 130 · 2015: 148 · 2014: 141 · 2013: 140 · 2012: 140
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut Universitaire de France
- National Institutes of Health (AA06420, AA08459, DK-26741)
- National Institute on Alcohol Abuse and Alcoholism (AA-06420, AA-08459)
- National Institute on Drug Abuse (DA04043, AA06420, R01DA004043)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- drug addiction, allostasis, relapse vulnerability, opponent process theory, stress response, compulsive drug taking, neural adaptation, homeostasis
- MeSH terms
- Animals, Humans, Hypothalamo-Hypophyseal System, Models, Neurological, Nerve Net, Pituitary-Adrenal System, Reinforcement, Psychology, Reward, Stress, Physiological, Substance Withdrawal Syndrome, Temperance, Behavior, Addictive, Substance-Related Disorders
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