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Consequences of post-weaning social isolation on anxiety behavior and related neural circuits in rodents
Open accessAbstract
Exposure to adverse experiences in early-life is implicated in the later vulnerability to development of psychiatric disorders, including anxiety and affective disorders in humans. Adverse early-life experiences likely impart their long-term consequences on mental health by disrupting the normal development of neural systems involved in stress responses, emotional behavior and emotional states. Neural systems utilizing the neurotransmitters serotonin, dopamine and the neuropeptide corticotropin-releasing factor (CRF) are implicated in mediating emotive behaviors, and dysfunction of these neurochemical systems is associated with mood/anxiety disorders. These neural systems continue maturing until early or mid-adolescence in humans, thus alterations to their development are likely to contribute to the long-term consequences of adverse early-life experiences. A large body of literature suggests that post-weaning isolation rearing of rodents models the behavioral consequences of adverse early-life experiences in humans. Overall, the majority findings suggest that post-weaning social isolation that encompasses pre-adolescence produces long-lasting alterations to anxiety behavior, while measures of monoaminergic activity in various limbic regions during social isolation suggest alterations to dopamine and serotonin systems. The goal of this review is to evaluate and integrate findings from post-weaning social isolation studies specifically related to altered fear and anxiety behaviors and associated changes in neuroendocrine function and the activity of monoaminergic systems.
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“Complete social isolation in adolescent rodents evokes widespread structural and functional changes in the brain, most prominently in neuromodulatory dopamine and serotonin systems and particularly within cortical and striatal targets.33, 36, 37”
From The effects of social deprivation on adolescent development and mental health (2020) · cites this paper as [37]
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“An advantage of rodent animal models such as mice and rats is that their development progresses through similar stages as human development.37”
From The effects of social deprivation on adolescent development and mental health (2020) · cites this paper as [37]
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“More specifically, although some divergent effects have been observed, the most consistent findings report that dopamine release in reward regions such as the nucleus accumbens increases following adolescent isolation, but dopamine activity in the prefrontal cortex decreases.33, 36, 37”
From The effects of social deprivation on adolescent development and mental health (2020) · cites this paper as [37]
In the citing paper
“By depriving animals of the play experiences that normally guide cortical development, post-weaning social isolation is conceptualized as a rodent model of adolescent adversity with long-lasting effects on neurobiology and behavior (Fone and Porkess, 2008; Lukkes et al., 2009; Robbins, 2016).”
From The effects of early life stress on reward processing (2018) · cites this paper as Lukkes et al., 2009
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“While pre-weaning maternal separation is often conceptualized as early life neglect and results in a depressive-like phenotype (Pryce et al., 2005), post-weaning social isolation during the juvenile and adolescent period produces sensory processing deficits and increases in fear and anxiety-like behavior (Fone and Porkess, 2008; Lukkes et al., 2009).”
From The effects of early life stress on reward processing (2018) · cites this paper as Lukkes et al., 2009
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Cited by
Sorted by citations
The effects of social deprivation on adolescent development and mental health
Orben, A., Tomova, L., & Blakemore, S.-J. (2020) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(20)30186-3 · Cited by 1,383
Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?
SPEAR, L. P. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.01.027 · Cited by 383
Neurobiology and consequences of social isolation stress in animal model—A comprehensive review
Mumtaz, F., Khan, M. I., Zubair, M., & Dehpour, A. R. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.05.086 · Cited by 369
Burke, A. R., McCormick, C. M., Pellis, S. M., & Lukkes, J. L. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.018 · Cited by 225
Self-citationStress in adolescence and drugs of abuse in rodent models: role of dopamine, CRF, and HPA axis
Burke, A. R., & Miczek, K. A. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3369-1 · Cited by 207
Metadata
- Authors
- Lukkes, J. L.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Lukkes, Jodi L.
- ORCID
- Lukkes, Jodi L.
- Venue
- Frontiers in Behavioral Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2009
- Volume
- 3
- Pages
- 18-18
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC2737489
- OpenAlex
- W2074801302
- Cited by
- 235
- References
- 138
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 23 · 2023: 16 · 2022: 13 · 2021: 20 · 2020: 19 · 2019: 10 · 2018: 15 · 2017: 13 · 2016: 8 · 2015: 10 · 2014: 12 · 2013: 13 · 2012: 9
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Foundation (CAREER)
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute on Drug Abuse (R01DA019921)
- National Center for Research Resources (P20RR015567)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- post-weaning social isolation, childhood adversity, anxiety-like behavior, fear behavior, monoaminergic systems, serotonin, dopamine, corticotropin-releasing factor, neuroendocrine function, limbic system, late childhood, psychiatric vulnerability, rodent models
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