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Review ArticleReview Article

The Flinders Sensitive Line Rat Model of Depression—25 Years and Still Producing

David H. Overstreet and Gregers Wegener
Lynette C. Daws, ASSOCIATE EDITOR
Pharmacological Reviews January 2013, 65 (1) 143-155; DOI: https://doi.org/10.1124/pr.111.005397
David H. Overstreet
Department of Psychiatry & Center for Alcohol Studies University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (D.H.O.); Centre for Psychiatric Research Aarhus University & Aarhus University Hospital, Risskov, Denmark (G.W.) and Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa (G.W.)
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Gregers Wegener
Department of Psychiatry & Center for Alcohol Studies University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (D.H.O.); Centre for Psychiatric Research Aarhus University & Aarhus University Hospital, Risskov, Denmark (G.W.) and Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa (G.W.)
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Lynette C. Daws
Department of Psychiatry & Center for Alcohol Studies University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (D.H.O.); Centre for Psychiatric Research Aarhus University & Aarhus University Hospital, Risskov, Denmark (G.W.) and Unit for Drug Research and Development, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa (G.W.)
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Abstract

Approximately 25 years have passed since the first publication suggesting the Flinders sensitive line (FSL) rat as an animal model of depression. At least 6 years of research on these rats was completed before that seminal paper, and there has been a steady stream of publications (130+) over the years. The present review will focus on several issues not previously covered in earlier reviews, summarize the several lines of ongoing investigations, and propose a novel mechanism that accounts for a number of previously unexplained observations. A key observation in the FSL rat relates to the antidepressant (AD)-like effects of known and putative antidepressants. The FSL rat typically exhibits an AD-like effect in behavioral tests for AD-like activity following chronic (14 days) treatment, although some studies have found AD-like effects after fewer days of treatment. In other observations, exaggerated swim test immobility in the FSL rat has been found to have a maternal influence, as shown by cross-fostering studies and observations of maternal behavior; the implications of this finding are still to be determined. Ongoing or recently completed studies have been performed in the laboratories of Marko Diksic of Canada, Aleksander Mathé of Sweden, Gregers Wegener of Denmark, Brian Harvey of South Africa, Paul Pilowsky and Rod Irvine of Australia, and Gal Yadid of Israel. Jennifer Loftis of Portland, Oregon, and Lynette Daws of San Antonio, Texas, have been working with the FSL rats in the United States. A puzzling feature of the FSL rat is its sensitivity to multiple chemicals, and its greater sensitivity to a variety of drugs with different mechanisms of action. It has been recently shown that each of these drugs feeds through G protein–coupled receptors to potassium-gated channels. Thus, an abnormality in the potassium channel could underlie the depressed-like behavior of the FSL rats.

Footnotes

  • This research was supported by The Danish Medical Research Council (Grant 11-107897), the Lundbeck Foundation, and Aarhus University Research Foundation (AU-IDEAS) (to G.W.).

  • dx.doi.org/10.1124/pr.111.005397

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 65 (1)
Pharmacological Reviews
Vol. 65, Issue 1
1 Jan 2013
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Review ArticleReview Article

FSL Rat Still Producing at 25

David H. Overstreet and Gregers Wegener
Pharmacological Reviews January 1, 2013, 65 (1) 143-155; DOI: https://doi.org/10.1124/pr.111.005397

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Review ArticleReview Article

FSL Rat Still Producing at 25

David H. Overstreet and Gregers Wegener
Pharmacological Reviews January 1, 2013, 65 (1) 143-155; DOI: https://doi.org/10.1124/pr.111.005397
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  • Article
    • Abstract
    • I. Introduction
    • II. Pre-model Findings
    • III. The Initial Model
    • Validity of FSL Model, Including Comparison with Other Animal Models of Depression
    • IV. Antidepressant-Like Effects
    • V. Social Interaction Test
    • VI. Maternal Effects
    • VII. Recent and Current Research
    • VIII. Novel Hypothesis—Changes in Potassium Channels Underlie Depressed-like Behavior of FSL Rats
    • IX. Conclusions
    • Acknowledgments
    • Authorship Contributions
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