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Prior Multiple Ethanol Withdrawals Enhance Stress-Induced Anxiety-Like Behavior: Inhibition by CRF1- and Benzodiazepine-Receptor Antagonists and a 5-HT1a-Receptor Agonist
Open accessAbstract
Repeated withdrawals from chronic ethanol induce a persistent adaptive change. Further, stress substitutes for the initial two withdrawals of a multiple-withdrawal protocol to sensitize rats to withdrawal-induced anxiety-like behavior ('anxiety'). Therefore, it was tested whether the persistent adaptation induced by multiple-withdrawal exposures allows stress to elicit anxiety after a period of abstinence. Social interaction was used to assess the degree of anxiety induced by 45 min of restraint stress 3, 7, or 14 days after rats were exposed to multiple withdrawals from a chronic 4.5% ethanol diet. Restraint stress reduced social interaction (ie anxiety-like behavior) at 3, but not at 7 or 14 days, after the multiple withdrawals. No anxiety response was observed in animals that received multiple withdrawals without stress or in animals that received stress when exposed only to control liquid diet. Drugs (ie a CRF1-receptor antagonist, a benzodiazepine receptor antagonist, and a 5-HT1A-receptor agonist) previously demonstrated to block the cumulative adaptation, when administered during repeated withdrawals, prevented stress-induced anxiety-like behavior during abstinence. Additionally, these drugs applied prior to stress in the rats previously exposed to the repeated withdrawal protocol, likewise, minimized stress-induced anxiety. The anxiety following stress during abstinence from previous chronic ethanol exposure is indicative of an interaction of stress with the persistent adaptive change caused by repeated withdrawals. Stress eliciting anxiety-like behavior during abstinence from previous ethanol exposures in rats is consistent with stress inducing anxiety during recovery (sobriety) in the alcoholic, a circumstance that can facilitate craving and relapse.
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“Systemic CRF 1 receptor antagonist administration blocked anxiety-like responses to alcohol withdrawal (Knapp et al., 2004;Overstreet et al., 2004b;Breese et al., 2005).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Breese et al., 2005
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Metadata
- Authors
- Breese, G. R., Overstreet, D. H., Knapp, D. J., & Navarro, M.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Breese, George R
- Venue
- Neuropsychopharmacology
- Published
- 2005-02-23
- Volume
- 30
- Issue
- 9
- Pages
- 1662-1669
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2864139
- OpenAlex
- W1979024772
- Cited by
- 124
- References
- 41
- Citations by year
- 2025: 2 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 10 · 2015: 6 · 2014: 10 · 2013: 8 · 2012: 6
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA014284, AA-14284, P50AA011605, AA 11605, R01AA014949, AA 14949, P60AA011605)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ethanol withdrawal, stress-induced anxiety, restraint stress, social interaction, CRF1 receptor antagonist, benzodiazepine antagonists, 5-HT1A receptor agonist, alcohol craving, relapse, alcoholism
- MeSH terms
- Ethanol, Analysis of Variance, Animals, Anxiety, Behavior, Animal, Buspirone, Central Nervous System Depressants, Drug Interactions, Flumazenil, Food, Formulated, Interpersonal Relations, Male, Pyrimidines, Pyrroles, Restraint, Physical, Stress, Psychological, Substance Withdrawal Syndrome, Time Factors, Anti-Anxiety Agents, Rats, Sprague-Dawley, Serotonin Receptor Agonists, Receptors, Corticotropin-Releasing Hormone, GABA Modulators, Rats
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