Altered explorative strategies and reactive coping style in the FSL rat model of depression

Abstract

Modeling depression in animals is based on the observation of behaviors interpreted as analog to human symptoms. Typical tests used in experimental depression research are designed to evoke an either-or outcome. It is known that explorative and coping strategies are relevant for depression, however these aspects are generally not considered in animal behavioral testing. Here we investigate the Flinders Sensitive Line (FSL), a rat model of depression, compared to the Sprague-Dawley (SD) rat in three independent tests where the animals are allowed to express a more extensive behavioral repertoire. The multivariate concentric square field™ (MCSF) and the novel cage tests evoke exploratory behaviors in a novel environment and the home cage change test evokes social behaviors in the re-establishment of a social hierarchy. In the MCSF test, FSL rats exhibited less exploratory drive and more risk-assessment behavior compared to SD rats. When re-exposed to the arena, FSL, but not SD rats, increased their exploratory behavior compared to the first trial and displayed risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL rats was more similar to that of SDs when the rats were familiar with the arena. In the novel cage test FSL rats exhibited a reactive coping style, consistent with the reduced exploration observed in the MCSF. Reactive coping is associated with less aggressive behavior. Accordingly, FSL rats displayed less aggressive behavior in the home cage change test. Taken together, our data show that FSL rats express altered exploratory behavior and reactive coping style. Reduced interest is a core symptom of depression, and individuals with a reactive coping style are more vulnerable to the disease. Our results support the use of FSL rats as an animal model of depression and increase our understanding of the FSL rat beyond the behavioral dimensions targeted by the traditional depression-related tests.

Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation

“…Still, there were more differences in the present study between trials 1 and 2 than between individuals tested repeatedly with 1 week intertest interval in adolescence (Lundberg et al, 2019). This indicates that the present finding could be more due to developmental effects since the memory effect can be assumed to be stronger with 1 week intertest interval than with 5 weeks, even though the memory effect in adulthood has been described with testing intervals between 1 and 6 weeks (Meyerson et al, 2006;Roman et al, 2007;Karlsson et al, 2009;Roman and Colombo, 2009;Magara et al, 2015).…”

Running Opposes the Effects of Social Isolation on Synaptic Plasticity and Transmission in a Rat Model of Depression

“…The selectively bred FSL rat strain is extensively used as an animal model for depression, and one of its characteristic behavior is increased sensitivity to stress [ 13 , 18 ]. One neurobiological mechanism associated with its depressed behavior is increased glutamate transmission and reduced plasticity in the hippocampus, conveyed by reduced levels of the glutamate transporter GLAST and reduced levels of D-serine [ 11 ].…”

Relevance of Rodent Models of Depression in Clinical Practice: Can We Overcome the Obstacles in Translational Neuropsychiatry?

“…Other tests that are gaining in popularity are based on natural behaviors, such as social interaction and/or the motivation to explore, rather than examining the response to a given stimulus or stressful situation. For example, our group and others have shown that decreased exploratory behavior is associated with a depression-like phenotype ( Kasahara et al, 2007 ; Li et al, 2010 ; Gómez-Galán et al, 2013 ; Magara et al, 2015 ). Several auxiliary tests can be used to obtain a more complete evaluation of an animal model or the response to a drug; in particular, tests for memory and anxiety are commonly used ( Lapiz-Bluhm et al, 2008 ).…”