ReviewThe Flinders Sensitive Line rat: A selectively bred putative animal model of depression
Section snippets
Initial development of lines
The original rationale behind the development of the Flinders Line rats was to create a strain/line of rats that was genetically resistant to the effects of the organophosphate anticholinesterase agent, diisopropyl fluorophosphate (DFP), so that the mechanisms involved could be compared with those involved in the development of tolerance to DFP (Russell and Overstreet, 1987). However, the selective breeding program led to the development of a strain/line of rats that was genetically more
Behavioral characteristics
In this section we discuss how closely the FSL rat resembles depressed individuals with regard to key behavioral symptoms, sleep parameters and associated variables, such as immune function, asthma, and inflammatory bowel disease (IBS).
Theoretical models
Hypotheses of the neurochemical basis of depressive disorders abound, so the present section will consider a limited number of theories, primarily those for which there are some data in the FSL rat that might permit a tentative conclusion.
Selective breeding strategy
The FSL and FRL rats were selectively bred using an outbreeding strategy that avoided matings between close relatives. Three responses to the anticholinesterase agent, diisopropyl fluorophosphate (DFP), were used: hypothermia, reduced water intake and reduced body weight (Overstreet et al., 1979). Six to ten mating pairs were used per generation and selection was applied for 30 generations. More recently, for at least 10 years, the FSL and FRL rat colonies have been maintained as closed
Therapeutic drugs
The FSL rat has been used to test for the antidepressant-like effects of classical antidepressants and selective serotonin reuptake inhibitors (SSRIs) as well as a variety of novel agents that presumably have different actions from the well-characterized antidepressants. This work has recently been summarized (Overstreet, 2002), so only a brief commentary on the previously published studies will be given. The remainder of this section will focus on the results that have been collected over the
Conclusions and future directions
Although the FSL rat exhibits several behaviors that are parallel to symptoms of depression in humans, there are also mismatches. The most notable examples are the anhedonia and cognitive disturbances in depressed individuals and normal reward-related behavior and food-motivated learning in FSL rats (Table 1). Whether these behaviors would be preferentially altered in FSL rats after exposure to stressors such as the CMS procedure, as was anhedonia (Pucilowski et al., 1993), remains to be
Acknowledgements
The generous financial support of the governments of Israel, Sweden, and the United States is acknowledged. We express our thanks to the many colleagues, graduate students and technicians who have assisted on the experiments described in this review paper.
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2022, Journal of EthnopharmacologyCitation Excerpt :Such studies will enable proof of concept and establish effective dose ranges for further pre-clinical and clinical evaluation. Considering genetic predisposition in the development of MDD (Dean and Keshavan, 2017; Jesulola et al., 2018), the Flinders Sensitive Line (FSL) rat is a genetic animal model that presents with robust construct, face, and predictive validity for MDD (Overstreet et al., 2005; Overstreet, 2012; Overstreet and Wegener, 2013). While the model is recognised to show preferential response to chronic antidepressants (Overstreet and Wegener, 2013), acute treatments have also been applied successfully (Du Jardin et al., 2018; Oberholzer et al., 2018).