Cited by 2,953Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesNeural and Behavioral Psychology Studies

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Drug Addiction, Dysregulation of Reward, and Allostasis

Koob, G·2001·Neuropsychopharmacology

DOI 10.1016/s0893-133x(00)00195-0

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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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Authors: Koob, G.
Affiliations: Scripps Research Institute (US)
Corresponding author: Koob, G
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2001-02
Volume: 24
Issue: 2
Pages: 97-129
ISSN: 0893-133X (ISSN-L)
DOI: 10.1016/s0893-133x(00)00195-0
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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Drug Addiction, Dysregulation of Reward, and Allostasis

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