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Increased Anxiety‐Like Behavior and Ethanol Self‐Administration in Dependent Rats: Reversal via Corticotropin‐Releasing Factor‐2 Receptor Activation
Abstract
Background: Corticotropin‐releasing factor (CRF) has been hypothesized to be one of the main regulators of the stress response observed during alcohol withdrawal. The CRF receptor subtypes seem to have a differential role in the regulation of stress‐related behavior. Given the behavioral characterization of these receptors, the objective of the following experiments was to characterize the role of CRF 2 receptors in the interaction between alcohol and stress by examining the effects of CRF 2 receptor activation in the behavioral stress response and ethanol self‐administration during early ethanol withdrawal in dependent rats. Methods: Male Wistar rats were made dependent on ethanol via chronic exposure to an ethanol containing liquid diet. Behavior in the elevated plus maze and ethanol self‐administration were measured at 2 hr after removal of the diet. The role of the CRF 2 receptor in the regulation of these behaviors during the early stages of withdrawal was examined via central injection of the highly selective CRF 2 receptor agonist urocortin 3. Results: Rats showed decreased exploration of the open arms of the elevated plus maze, an indication of a heightened behavioral stress response, after chronic ethanol exposure. This effect was attenuated by central injection of urocortin 3. In addition, urocortin 3 injections reversed the increase in ethanol self‐administration observed during early withdrawal in dependent rats. Conclusions: Reversal of the increased stress‐related behavior in the elevated plus maze observed after injections of urocortin 3 indicates that the decreased responding for ethanol also seen after urocortin 3 administration is likely due to a diminished anxiety‐like state. These data suggest that activation of the CRF 2 receptor may provide a novel target in the attenuation of the stress response characteristic of the early stages of ethanol withdrawal.
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“Nonselective CRF antagonists, as well as CRF-R1 antagonists, selectively block excessive consumption of several drugs of abuse in dependent rats, but not in non-dependent rats (Valdez et al 2004; Funk et al 2006; Funk et al 2007).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Valdez et al 2004
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“However, a CRF-R2 agonist also blocked excessive alcohol consumption in dependent rats, suggesting opposite roles for these two receptors (Valdez et al 2004).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Valdez et al 2004
In the citing paper
“CRF-R1 activation mediates many of these stress effects in rats, while CRF-R2 activation is alternately the same as CRF-R1, opposing CRF-R1, or ineffective in modulating stress, depending on the assay and the brain region (Ho et al 2001; Takahashi et al 2001; Valdez et al 2004; Zhao et al 2007; for a review see Heinrichs and Koob, 2004).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Valdez et al 2004
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Metadata
- Authors
- Valdez, G. R., Sabino, V., & Koob, G. F.
- Affiliations
- Scripps Research Institute (US)
- University of Palermo (IT)
- Corresponding author
- Valdez, Glenn R.
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2004-06
- Volume
- 28
- Issue
- 6
- Pages
- 865-872
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- OpenAlex
- W1997296561
- Cited by
- 131
- References
- 70
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 9 · 2018: 3 · 2017: 4 · 2016: 8 · 2015: 7 · 2014: 11 · 2013: 4 · 2012: 8
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f31aa005563-02)
- National Institute on Alcohol Abuse and Alcoholism (AA12602, AA05563, AA-08459, R01AA012602)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- urocortin 3, ethanol withdrawal, anxiety-like behavior, ethanol self-administration, behavioral stress response, alcoholism, elevated plus maze, alcohol withdrawal treatment
- MeSH terms
- Ethanol, Alcoholism, Animals, Anxiety, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Exploratory Behavior, Male, Self Administration, Substance Withdrawal Syndrome, Rats, Wistar, Receptors, Corticotropin-Releasing Hormone, Rats, Urocortins
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