The DOI matches its Crossref record; 229 of the 229 references it cites were found in a registry or an index.
Conceptual framework for the etiology of alcoholism: a “kindling”/stress hypothesis
Open accessAbstract
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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“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).”
From Impulsivity, frontal lobes and risk for addiction (2009) · cites this paper as Breese et al., 2005
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Research works printed but not linked: 3
- 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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“…of ethanol exposure and withdrawal, support the idea that progressively worsening profiles of withdrawal-like states arise and may persist over time to render subjects vulnerable to future environmental stressors and challenges (Breese et al., 2005b; Overstreet et al., 2002; Valdez et al., 2002).”
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Metadata
- 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
- Published
- 2004-10-23
- Volume
- 178
- Issue
- 4
- Pages
- 367-380
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- 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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