Behavioural characterisation of chronic unpredictable stress based on ethologically relevant paradigms in rats.

The chronic unpredictable stress (CUS) paradigm is extensively used in preclinical research. However, CUS exhibits translational inconsistencies, some of them resulting from the use of adult rodents, despite the evidence that vulnerability for many psychiatric disorders accumulates during early life. Here, we assessed the validity of the CUS model by including ethologically-relevant paradigms in juvenile rats. Thus, socially-isolated (SI) rats were submitted to CUS and compared with SI (experiment 1) and group-housed controls (experiment 1 and 2). We found that lower body-weight gain and hyperlocomotion, instead of sucrose consumption and preference, were the best parameters to monitor the progression of CUS, which also affected gene expression and neurotransmitter contents associated with that CUS-related phenotype. The behavioural characterisation after CUS placed locomotion and exploratory activity as the best stress predictors. By employing the exploratory factor analysis, we reduced each behavioural paradigm to few latent variables which clustered into two general domains that strongly predicted the CUS condition: (1) hyper-responsivity to novelty and mild threats, and (2) anxiety/depressive-like response. Altogether, the analyses of observable and latent variables indicate that early-life stress impairs the arousal-inhibition system leading to augmented and persistent responses towards novel, rewarding, and mildly-threatening stimuli, accompanied by lower body-weight gain.

Individual differences in the forced swimming test and the effect of environmental enrichment: searching for an interaction.

Animals with low and high immobility in the forced swimming test (FST) differ in a number of neurobehavioral factors. A growing body of evidence suggests that the exposure to enriched environments mediates a number of changes in the brain. Therefore, we studied if animals' individuality can somehow modulate the response to environmental stimuli. Male rats were classified according to their immobility time scores in the FST test session as animals with low, medium or high immobility. Then, rats from groups with low and high immobility were randomly distributed in two groups to be reared in different housing conditions (i.e., enriched and standard conditions) during 8weeks. Animals were subjected to the open field test (OFT) before and 6weeks after the start of housing protocol. Rats with high immobility in the FST also showed high ambulation and high rearing time in the first OFT. Such findings were not observed in the second OFT. Conversely, an effect of environmental enrichment was found in the second OFT where enriched animals showed lower ambulation and higher grooming time than the standard control group. Rats were sacrificed after the housing protocol and neurochemical content and/or gene expression were studied in three different brain regions: the prefrontal cortex, the hippocampus and the nucleus accumbens. Rats with low immobility showed significantly higher accumbal 5-HT levels than animals with high immobility, whereas no neurochemical differences were observed between enriched and standard animals. Regarding expression data, however, an effect of enrichment on accumbal corticotropin-releasing factor (CRF) and its receptor 1 (CRFR1) levels was observed, and such effect depended on immobility levels. Thus, our results not only allowed us to identify a number of differences between animals with low and high immobility or animals housed in standard and enriched conditions, but also suggested that animals' individuality modulated in some way the response to environmental stimuli.