Blunted accumbal dopamine response to cocaine following chronic social stress in female rats: exploring a link between depression and drug abuse
Open accessAbstract
Rationale Women have twice the risk as men to develop depression. Approximately, 24% of major depression disorder cases have comorbid disorders with substance abuse. Several central systems, including dopaminergic and serotonergic pathways, are thought to be involved in such comorbidity. Objectives The present study established a chronic social stress model in female rats, which produces some cardinal features of depressive-like symptoms. Further, we examined the effects of acute cocaine on dopamine (DA) and serotonin (5-HT) in the nucleus accumbens (NAc) using this model. Methods Female Long-Evans rats confronted a nursing dam in its home cage for 30 min twice daily for 21 days. The non-stressed control group was handled daily throughout the experiment. During the 21 days of stress, behaviors during confrontations, weight, preference for saccharin, and estrous cycles were measured. Ten days after the last confrontation, the experimental rat was challenged with 10 mg/kg of cocaine, and levels of DA and 5-HT in the NAc were measured using in vivo microdialysis. Results During the course of daily confrontations for 21 days, the experimental females significantly increased the duration of immobility, reduced weight gain and the preference for saccharin, and disrupted estrous cycles during the stress. Chronic social stress significantly attenuated cocaine-induced DA levels, and to some extent, attenuated a percent change of 5-HT compared to the non-stressed control group. Conclusions Chronic social defeat stress for 21 days induced physiological and behavioral depression-relevant deficits and blunted response of dopaminergic and to some extent, serotonergic neurons to cocaine challenge in females.
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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 Shimamoto et al., 2011
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References 76 · Cited by 81
Research works printed but not linked: 4
- Covington HE III Miczek KA Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration “binges” Psychopharmacology 2001 158 388 398 11797060
- Fuchs E Flügge G Social stress in tree shrews: effects on physiology, brain function, and behavior of subordinate individuals Pharmacol Biochem Behav 2002 73 247 258 12076743
- Kessler RC Berglund P Demler O Jin R Koretz D Merikangas KR Rush AJ Walters EE Wang PS The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R) JAMA 2003 289 3095 3105 12813115
- National Research Council Guide for the care and use of laboratory animals 2010 The National Academies Press Washington, D.C
- Authors
- Shimamoto, A., DeBold, J. F., Holly, E. N., & Miczek, K. A.
- Affiliations
- Tufts University (US)
- Corresponding author
- Shimamoto, Akiko
- Venue
- Psychopharmacology
- Published
- 2011-06-03
- Volume
- 218
- Issue
- 1
- Pages
- 271-279
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC3901580
- OpenAlex
- W1983353697
- Cited by
- 81
- References
- 76
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 1 · 2019: 3 · 2018: 7 · 2017: 8 · 2016: 5 · 2015: 5 · 2014: 16 · 2013: 6 · 2012: 8
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R37AA005122)
- National Institute on Drug Abuse (R01DA002632, DA-002632, R01DA031734)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- chronic social stress, social defeat stress, depression, cocaine, dopamine, serotonin, nucleus accumbens, female rats, estrous cycle, saccharin preference, immobility
- MeSH terms
- Animals, Behavior, Animal, Body Weight, Cocaine, Depression, Disease Models, Animal, Dopamine, Female, Nucleus Accumbens, Saccharin, Serotonin, Sex Factors, Microdialysis, Rats, Long-Evans, Estrous Cycle, Rats
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