Helplessness-like escape deficits of NIH-HS rats predict passive behavior in the forced swimming test: Relevance for the concurrent validity of rat models of depression

Abstract

The genetically heterogeneous NIH-HS rat stock has been characterized by its response to anxiety-and fear-inducing situations, thus leading to the conclusion that they are a rather anxious and passive coping type of rats. Taking advantage of these profiles, and knowing that they show very poor performance in the two-way active (shuttle box) escape/avoidance task, we have tested NIH-HS rats (n = 80) in the forced swimming test (FST) as well as we have studied escape response deficits (i.e. response failures) of the same animals in the two-way shuttle box task. They were also tested for anxiety in the elevated zero-maze. The goal of such a study was that of investigating whether there are associations or relationships among helplessness-like or passive coping responses between both models of depression, i.e. the FST and the helplessness-like escape deficits in the shuttle box task. The results for the first time show associations among responses from both depression models and that selecting rats for displaying extreme (active or passive) responses in one of the models predict in a coherent manner (according to the hypothesis) their behaviour in the other model. These findings are discussed in the context of the concurrent validity of both models of depression as well as concerning the possible relevance of NIH-HS rats as a tool for future studies on this field.

Spatial learning in the genetically heterogeneous NIH-HS rat stock and RLA-I/RHA-I rats: Revisiting the relationship with unconditioned and conditioned anxiety

“…That study demonstrated that the procedure used to generate the genetically heterogeneous stock had been successful, since for most traits related to consumption/effects of ethanol, NIH-HS rats fell approximately in the middle of the high and low values of the eight inbred progenitor strains [5,6]. The neurobehavioral characterization of NIH-HS rats carried out so far in our laboratory includes traits related to unconditioned and conditioned anxiety/fear, exploratory behavior and coping style, as well as hormonal sensitivity to stress and central gene expression [7][8][9][10][11][12][13][14][15][16][17][18]. These studies have led to the conclusion that the genetically heterogeneous rat stock displays relatively elevated anxiety/fear (as shown by unlearned and learned anxiety tests/tasks) and enhanced hormonal responses to stress, as well as a predominantly reactive (i.e.…”

Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia

“…The genetically heterogeneous NIH-HS rat stock (i.e., “National Institutes of Health Genetically Heterogeneous Rat Stock”) was developed by Hansen and Spuhler ( 1984 ) through an eight-way cross from eight inbred rat strains and they were bred for more than 50 generations. The NIH-HS rats are a unique tool to study the genetic basis of complex traits due to their broad phenotypic variation and high degree of genetic recombination compared to the usual laboratory rat strains (e.g., Spuhler and Deitrich, 1984 ; López-Aumatell et al, 2008 , 2009a , b , 2011 ; Johannesson et al, 2009 ; Vicens-Costa et al, 2011 ; Díaz-Morán et al, 2012 , 2013a , b , c , 2014 ; Baud et al, 2013 , 2014a , b ; Estanislau et al, 2013 ; Palència et al, 2013 ; Alam et al, 2014 ; Tsaih et al, 2014 ). Moreover, NIH-HS rats have been shown to closely resemble RLA-I rats in their coping style and stress sensitivity profiles (e.g., López-Aumatell et al, 2009a ; Díaz-Morán et al, 2012 , 2013c ; Estanislau et al, 2013 ).…”

Individual responses of rodents in modelling of affective disorders and in their treatment: prospective review

“…However, a few studies that observed individual animals suggest that this may be an advantageous approach and that it might be possible to predict the response of a specific animal to a challenge based on its response to other challenges. For example, working with NIH-HS rats, researchers examined helplessness-like escape deficits in a shuttle box and behaviour in the forced swimming test (FST) and showed that at least for the extreme animals, the behaviour in one test predicts the behaviour in the other model (Table 1) (66).…”