Factor analysis of Forced Swimming test, Sucrose Preference test and Open Field test on enriched, social and isolated reared rats

Abstract

Developmental and social factors are known to play a crucial role in the pathogenesis of affective disorders. Although it has been demonstrated that early life aversive experiences can be a risk factor in the development of human depression, most of the investigation in animals that try to model depression do not include postnatal manipulations. Since housing represents a fundamental ethological factor which modifies behavior and brain development, this study aimed to investigate the impact of different social and structural housing conditions on the development of a depressive-like syndrome in the behavioral despair paradigm and an anxiety-like syndrome in the unconditioned anxiety paradigm. The present study uses several multivariate analyses to study the impact of housing conditions in animal models of depression and anxiety. In this study, social isolation was able to reproduce the effects found in other animals models based on stress, suggesting that only 2 months of social isolation are enough to produce effects that can be useful as behavioral model of depression. Moreover, environmental enrichment showed an antidepressive and anxiolytic like effect in animal models of depression and anxiety. This effect, which has not been reported in earlier studies, suggests that stimulation during the first stages of growth might play a “protective” role on behavior and brain development.

Introduction

The environments in which human infants and children grow are fundamental to determine their progress. Several aversive situations like parental loss, emotional and physical neglect, and abuse have been shown to be associated with the risk of suffering psychological disorders across the life span [47]. Although it has been demonstrated that early life aversive experiences can be a risk factor in the development of human depression [30], [41], most of the investigations in animals that try to model depression do not include postnatal manipulations. However, specific manipulations of the postnatal social environment in rats can result in chronic developmental changes, such that, when studied in terms of behavior and physiology under basal and laboratory test conditions [47], [49], they provide important models of specific symptoms and associated abnormalities in depression or anxiety [48], [49], [53]. The association between environment factors and the appearance of abnormal behaviors has motivated the design of devices and techniques for enrichment or impoverishment of the animals’ environments.

Environmental enrichment, that can be achieved using objects and several cage designs to improve the quality of life of the laboratory animal [18], have shown that animals that are reared in these conditions, display lower basal activity in an inescapable novel environment relative to animals housed in an impoverished condition [3]. On the other hand, social isolation may have long-term consequences for the animal. It has been demonstrated that when comparing socially isolated rats (SI) with environmentally enriched rats (EE), SI animals generally show higher states of fearfulness, and become more responsive and vulnerable to environmental changes [14], [15], [21], [22], [23]. Thus, social isolation may be considered as a long-term stressor and environmental impoverishment [29], [49], [54], [60]. With regard to the latter, in our recent study (unpublished data) we show that chronic exposure of rats to an enriched environment improves behavior using depression and anxiety models. Moreover, this condition increased brain weight and the cortical size compared with the social isolated group. The aim purpose of this study is to estimate the construct and predictive validity of housing condition effects on depression and anxiety models, using following multivariate statistical analyses:

• Factor analysis (principal components) to identify factors that could explain the possible patterns of correlation between the superficial variables (variables directly measured). It was expected that the behaviors measured would be clustered according to the behavioral test to which they belong (Forced Swimming test, Open Field test and Sucrose Preference test), to confirm that the behavioral variables were related to the theoretical construct underlying each test.

• Multivariate variance analysis (MANOVA) to compare the factorial loads between groups (enrichment, standard control and Social Isolation), with the main purpose to determine if housing conditions are able to produce significant differences in the factors extracted

• Linear regression analysis to estimate how the extracted factors were predicted and explained by the housing conditions. Additionally, this analysis was used to estimate the weight on the factor loads that each behavior has.

Finally, and taking into account all the analyses, validity of the housing conditions will be discussed, and the extent to which postnatal environmental manipulations induce long-term behavioral states that may be analogous to symptoms and associated abnormalities of depression and anxiety.