Cocaine Experience Establishes Control of Midbrain Glutamate and Dopamine by Corticotropin-Releasing Factor: A Role in Stress-Induced Relapse to Drug Seeking
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Footshock stress can reinstate cocaine-seeking behavior through a central action of the stress-associated neurohormone corticotropin-releasing factor (CRF). Here we report (1) that footshock stress releases CRF in the ventral tegmental area (VTA) of the rat brain, (2) that, in cocaine-experienced but not in cocaine-naive rats, this CRF acquires control over local glutamate release, (3) that CRF-induced glutamate release activates the mesocorticolimbic dopamine system, and (4) that, through this circuitry, footshock stress triggers relapse to drug seeking in cocaine-experienced animals. Thus, a long-lasting cocaine-induced neuroadaptation, presumably at the level of glutamate terminals in the VTA, appears to play an important role in stress-induced relapse to drug use. Similar neuroadaptations may be important for the comorbidity between addiction and other stress-related psychiatric disorders.
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Stress causes CRF release into the VTA and NAC shell, and this CRF acts on CRF receptors to induce reinstatement of drug seeking.
“Using stress-induced reinstatement of drug seeking, it has been demonstrated that stress causes CRF release into the VTA and NAC shell (Wang et al 2005; Chen et al 2012a), and this CRF release acts on CRF receptors to induce reinstatement (Ungless et al 2003; Wang et al 2005; Wang et al 2007; Blacktop et al 2011).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Wang et al 2005
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- Authors
- Wang, B., Shaham, Y., Zitzman, D., Azari, S., Wise, R. A., & You, Z.-B.
- Affiliations
- National Institutes of Health (US)
- Tufts University (US)
- Corresponding author
- Wise, Roy A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-06-01
- Volume
- 25
- Issue
- 22
- Pages
- 5389-5396
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725007
- OpenAlex
- W2139476920
- Cited by
- 369
- References
- 49
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 14 · 2021: 11 · 2020: 29 · 2019: 11 · 2018: 20 · 2017: 11 · 2016: 19 · 2015: 24 · 2014: 23 · 2013: 25 · 2012: 27
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- cocaine, corticotropin-releasing factor, footshock stress, ventral tegmental area, glutamate release, dopaminergic system, mesocorticolimbic pathway, neural adaptation, addiction, stress-related psychiatric disorders
- MeSH terms
- Animals, Corticotropin-Releasing Hormone, Dopamine, Male, Recurrence, Stress, Physiological, Microdialysis, Ventral Tegmental Area, Glutamic Acid, Cocaine-Related Disorders, Rats, Long-Evans, Rats
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