Cited by 124Neurotransmitter Receptor Influence on BehaviorStress Responses and CortisolNeuropeptides and Animal Physiology

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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

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Breese, George R, Overstreet, David H, Knapp, Darin J, Navarro, Montserrat·2005·Neuropsychopharmacology

DOI 10.1038/sj.npp.1300706PMC PMC2864139

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Abstract

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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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.
Overstreet DH, Knapp DJ, Breese GR (2004a). Brain site-selective effects of 5-HT1A agonist and 5-HT2C antagonist on ethanol withdrawal induced anxiety. Alcohol Clin Exp Res 28: 64A.

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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
ORCID: Breese, George R
Navarro, Montserrat
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2005-02-23
Volume: 30
Issue: 9
Pages: 1662-1669
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1300706
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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Prior Multiple Ethanol Withdrawals Enhance Stress-Induced Anxiety-Like Behavior: Inhibition by CRF1- and Benzodiazepine-Receptor Antagonists and a 5-HT1a-Receptor Agonist

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