Long‐term behavioral and neurochemical effects of chronic stress exposure in rats
Open accessAbstract
Rats exposed to acute unavoidable stress develop a deficit in escaping avoidable aversive stimuli that lasts as long as unavoidable stress exposure is repeated. A 3‐week exposure to unavoidable stress also reduces dopamine (DA) output in the nucleus accumbens shell (NAcS). This study showed that a 7‐day exposure to unavoidable stress induced in rats an escape deficit and a decrease in extraneuronal DA basal concentration in the NAcS. Moreover, animals had reduced DA and serotonin (5‐HT) accumulation after cocaine administration in the medial pre‐frontal cortex (mPFC) and NAcS, compared with control animals. After a 3‐week exposure to unavoidable stress, escape deficit and reduced DA output in the NAcS were still significant at day 14 after the last stress administration. In the mPFC we observed: (i) a short‐term reduction in DA basal levels that was back to control values at day 14; (ii) a decrease in DA accumulation at day 3 followed by a significant increase beyond control values at day 14; (iii) a significant reduction in 5‐HT extraneuronal basal levels at day 3, but not at day 14. Finally, a significant decrease in 5‐HT accumulation following cocaine administration was present in the NAcS and mPFC at day 3, but not at day 14. In conclusion, a long‐term stress exposure induced long‐lasting behavioral sequelae associated with reproducible neurochemical modifications.
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Unavoidable stress administered over one week and three weeks was associated with a decrease in nucleus accumbens dopamine output.
“whilst unavoidable stress administered over one week and three weeks was associated with a decrease in nucleus accumbens dopamine output (Mangiavacchi et al., 2001).”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Mangiavacchi et al., 2001
Exposure to repeated longer-term stressors leads to decreases in striatal dopamine function including nucleus accumbens dopamine output, reduced cocaine-induced nucleus accumbens dopamine release, and reduced striatal dopamine receptor availability.
“Exposure to repeated longer-term stressors leads to decreases in striatal dopamine function including nucleus accumbens dopamine output (Mangiavacchi et al., 2001), reduced cocaine-induced nucleus accumbens dopamine release (Shimamoto et al., 2011; Holly and Miczek, 2016), and reduced striatal dopamine receptor availability (Meaney et al., 2002; Brake et al., 2004).”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Mangiavacchi et al., 2001
Decreased DA release to the NAc occurs after exposure to chronic repeated or unavoidable stress in rats, suggesting that stress significantly reduces mesolimbic DA transmission in rodent models.
“Decreased DA release to the NAc has been shown to occur after exposure to chronic repeated or an unavoidable stress regimen in rats [189,197,198], suggesting that stress significantly reduces mesolimbic DA transmission in rodent models.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [198]
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References 41 · Cited by 137
Research works printed but not linked: 3
- Di Chiara G. and Imperato A. (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Natl Acad. Sci. USA 85, 5274±5278.
- Paxinos G. and Watson C. (1986) The Rat Brain in Stereotaxic Coordinates, 2nd Edn. Academic Press, New York.
- Yoshioka M., Matsumoto M., Togashi H. and Saito H. (1996) Effect of conditioned fear stress on dopamine release in the rat prefrontal cortex. Neurosci. Lett. 209, 301±203. Dopamine and 5-HT output after chronic stress 1121 q 2001 International Society for Neurochemistry, Journal of Neurochemistry, 79, 1113±1121 14714159, 2001, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2001.00665.x by Mount Vernon Nazarene University, Wiley Online Library on [17/08/2026]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License · DOI
- Authors
- Mangiavacchi, S., Masi, F., Scheggi, S., Leggio, B., De Montis, M. G., & Gambarana, C.
- Affiliations
- University of Siena (IT)
- Corresponding author
- Gambarana, Carla
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2001-12-15
- Volume
- 79
- Issue
- 6
- Pages
- 1113-1121
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1522864766
- Cited by
- 137
- References
- 41
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 7 · 2014: 10 · 2013: 2 · 2012: 7
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Funders
- International Society for Neurochemistry
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- chronic stress, escape deficit, dopamine, serotonin, nucleus accumbens shell, medial prefrontal cortex, serotonin accumulation, long-term behavioral effects, neurochemical changes
- MeSH terms
- Animals, Chronic Disease, Cocaine, Dopamine, Escape Reaction, Helplessness, Learned, Male, Nucleus Accumbens, Restraint, Physical, Scopolamine, Serotonin, Stress, Physiological, Time Factors, Rats, Sprague-Dawley, Prefrontal Cortex, Microdialysis, Muscarinic Antagonists, Dopamine Uptake Inhibitors, Rats
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