Cited by 60Stress Responses and CortisolTryptophan and brain disordersNeuropeptides and Animal Physiology

Cytokine involvement in stress may depend on corticotrophin releasing factor to sensitize ethanol withdrawal anxiety

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Knapp, Darin J., Whitman, Buddy A., Wills, Tiffany A., Angel, Robert A., Overstreet, David H., Criswell, Hugh E., Ming, Zhen, Breese, George R.·2011·Brain, Behavior, and Immunity

Abstract

Stress has been shown to facilitate ethanol withdrawal-induced anxiety. Defining neurobiological mechanisms through which stress has such actions is important given the associated risk of relapse. While CRF has long been implicated in the action of stress, current results show that stress elevates the cytokine TNFα in the rat brain and thereby implicates cytokines in stress effects. In support of this view, prior TNFα microinjection into the central amygdala (CeA) of rats facilitated ethanol withdrawal-induced anxiety-a response that could not be attributed to an increase in plasma corticosterone. To test for a possible interaction between cytokines and CRF, a CRF1-receptor antagonist (SSR125543) administered prior to the repeated administration of TNFα or MCP-1/CCL2 reduced the magnitude of the withdrawal-induced anxiety. This finding provided evidence for cytokine action being dependent upon CRF. Additionally, the sensitizing effect of stress on withdrawal-induced anxiety was reduced by treating the repeated stress exposure prior to ethanol with the MEK inhibitor SL327. Consistent with cytokines having a neuromediator function distinct from a neuroimmune action, TNFα increased firing rate and GABA release from CeA neurons. Thus, an interaction of glial and neuronal function is proposed to contribute to the interaction of stress and chronic ethanol. Interrupting this potential glial-neuronal interaction could provide a novel means by which to alter the development of emotional states induced by stress that predict relapse in the alcoholic.

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Crossref · 10.1016/j.bbi.2011.02.018

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Authors
Knapp, D. J., Whitman, B. A., Wills, T. A., Angel, R. A., Overstreet, D. H., Criswell, H. E., Ming, Z., & Breese, G. R.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Knapp, Darin J.
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2011-06
Volume
25
Pages
S146-S154
ISSN
0889-1591 (ISSN-L)
OpenAlex
W2125222220
Cited by
60
References
78
Citations by year
2026: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 9 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 1
FWCI
1.63
Type
journal article
Language
en
Open access
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • Sanofi
  • National Institute on Alcohol Abuse and Alcoholism (P50AA011605, R01AA014949, AA011605, AA 14949, R01AA017462, AA017462, P60AA011605)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
stress, corticotropin-releasing factor, cytokines, TNF-α, CCL2/MCP-1, CRF1 receptor antagonist, central amygdala, MEK inhibition, SL327, GABA release, neuron-glia interactions, relapse, chronic ethanol exposure
MeSH terms
Adaptation, Psychological, Ethanol, Alcohols, Amygdala, Analysis of Variance, Animals, Anxiety, Corticosterone, Corticotropin-Releasing Hormone, Electrophysiology, Hydrocarbons, Halogenated, Male, Microinjections, Restraint, Physical, Stress, Physiological, Substance Withdrawal Syndrome, Thiazines, Tumor Necrosis Factor-alpha, Cytokines, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Rats

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