Cited by 167Substance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on BehaviorAlcohol Consumption and Health Effects

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Conceptual framework for the etiology of alcoholism: a “kindling”/stress hypothesis

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Breese, George R., Overstreet, David H., Knapp, Darin J.·2005·Psychopharmacology

DOI 10.1007/s00213-004-2016-2PMC PMC2958094

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Abstract

Rationale The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse.Objective and results An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence--a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis.Conclusions The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse--and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.

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The European NEAT Program: An Integrated Approach Using Acamprosate and Psychosocial Support for the Prevention of Relapse in Alcohol‐Dependent Patients With a Statistical Modeling of Therapy Success Prediction
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Subtypes of Alcohol‐Dependent Men: A Typology Based on Relative Genetic and Environmental Loading
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An examination of the tension reduction hypothesis: The relationship between anxiety and alcohol in college students
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Herbal Remedies for Alcoholism: Promises and Possible Pitfalls
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Self-citation
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Breese GR, Knapp DJ, Overstreet DH (2004b) Stress-induced anxiety-like behavior during abstinence from previous chronic ethanol exposure. Alcohol Clin Exp Res 28:191A
Knapp DJ, Overstreet DH, Breese GR (2003) CRF and benzodiazepine antagonists modulate restraint stress sensitization of alcohol-withdrawal anxiety. Alcohol Clin Exp Res 27:98A
Knapp DJ, Angel RA, Overstreet DH, Breese GR (2004a) The prophylactic effects of flumazenil on repeated ethanol withdrawal-induced anxiety are mediated by the amygdala. Alcohol Clin Exp Res 28:142A

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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
“Studies in animals have found that repeated drinking and withdrawal-abstinence cycles causes a progressive adaptive change to increase anxiety and negative affect, apparently through amygdale activation(Breese et al., 2005).”
Background
A key role for corticotropin-releasing factor in alcohol dependence
Heilig, M., & Koob, G. F. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.006 · Cited by 503
REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?
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The dark side of emotion: the addiction perspective
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See all 167

Authors: Breese, G. R., Overstreet, D. H., & Knapp, D. J.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Breese, George R.
ORCID: Breese, George R.
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2004-10-23
Volume: 178
Issue: 4
Pages: 367-380
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-004-2016-2
PMC: PMC2958094
OpenAlex: W2064332293
Cited by: 167
References: 229
Citations by year: 2026: 1 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 10 · 2018: 1 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 12 · 2013: 13 · 2012: 9
FWCI: 6.23
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (1z01aa000243-02)
National Institute on Alcohol Abuse and Alcoholism (R01AA014284, AA-14284, P50AA011605, AA 11605, R01AA014949, Z01AA000214, AA00243, R01AA012655, AA 00214, AA 14949, K21AA000214, K05AA000253, AA-12655, P60AA011605)
Topics: Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords: etiology of alcoholism, kindling, stress, neural adaptation, relapse, alcohol withdrawal, voluntary alcohol drinking, chronic ethanol exposure, anxiety-like behavior
MeSH terms: Adaptation, Physiological, Alcoholism, Animals, Humans, Kindling, Neurologic, Species Specificity, Stress, Physiological

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Conceptual framework for the etiology of alcoholism: a “kindling”/stress hypothesis

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