The DOI matches its Crossref record; 165 of the 170 references it cites were found in a registry or an index.
The flinders sensitive line rats: A genetic animal model of depression
Abstract
The Flinders Sensitive Line (FSL) rat, selectively bred for increased responses to the anticholinesterase DFP, was originally proposed as an animal model of depression because, like depressed humans, it is supersensitive to the behavioral and hormonal effects of cholinergic (muscarinic) agonists. The present review critically examines earlier and recent data collected on FSL rats to assess whether the model has good face, construct and/or predictive validity. With respect to face validity, FSL rats resemble depressed humans, at least superficially, in that they demonstrate: (a) reduced locomotor activity, (b) reduced body weight, (c) increased REM sleep, and (d) cognitive (learning) difficulties. So far, studies designed to assess the presence of anhedonia, a cardinal symptom of melancholic depression, have been inconclusive, but there are trends for the FSL rats to be more anhedonic than their control counterparts, the Flinders Resistant Line (FRL) rats, when exposed to chronic mild stress. Thus, FSL rats fulfill the criterion of face validity. Because FSL rats also are more sensitive to cholinergic agonists and have phase advanced circadian rhythms, they meet the criteria for the cholinergic and circadian rhythm models of depression and, therefore, have good construct validity. A key behavioral symptom exhibited by the FSL rat is demonstration of an exaggerated immobility when exposed to stressors such as foot shock and forced swimming. This behavioral abnormality has been normalized by a number of well-recognized antidepressant drugs such as imipramine and desipramine, as well as newer generation antidepressants with promising clinical effects such as sertraline and rolipram. However, several treatments that have not been routinely used to treat depression (lithium, exposure to bright light, the anticholinesterase DFP) have been ineffective in reversing the exaggerated immobility. Thus, the evidence in the present review indicates that the FSL rat model of depression fulfills the criteria of face, construct, and predictive validities.
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“In rodent studies, the Flinders rat model was selected for its sensitivity to challenge with an AChE inhibitor, and sensitive rats also display a constellation of depression-like endophenotypes, supporting the idea that increasing ACh levels increases symptoms of depression (Overstreet, 1993).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Overstreet, 1993
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“Importantly, the FSL rats had higher levels of anxiety and depressive-like behavior that were like those obtained in the LY subline of rats (Overstreet, 1993; Overstreet et al., 2005; Eguibar et al., 2017b).”
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Metadata
- Authors
- Overstreet, D. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Overstreet, David H.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 1993-03
- Volume
- 17
- Issue
- 1
- Pages
- 51-68
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1991527095
- Cited by
- 369
- References
- 170
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 5 · 2018: 10 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 8 · 2013: 18 · 2012: 9
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- Flinders Sensitive Line rats, animal models of depression, anhedonia, chronic mild stress, immobility, antidepressant efficacy, circadian rhythm, locomotor activity, REM sleep, face validity, construct validity, predictive validity
- MeSH terms
- Animals, Depression, Disease Models, Animal, Rats, Inbred Strains, Rats
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