Search

Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces detrimental effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first postnatal days and exposure to a substitute mother. The maternal care of biological and substitute mothers was measured. The male and female offspring were evaluated during adulthood in several contexts. Anxiety was measured by the elevated plus-maze (EPM), acoustic startle response (ASR) and forced swim test (FST). In other group of animals, novelty-seeking was measured (activity in an inescapable novel environment, preference for novel environments and exploration of novel objects). Plasmatic ACTH and corticosterone in basal conditions and in response to stress were also measured. Cognitive impulsivity was assessed by a delay-discounting paradigm, and impulsive action, attention and compulsive-like behaviour by a five choice serial reaction time task (5CSRTT). ELS decreased pup body weight and increased the care of the biological mother; however, the substitute mother did not exhibit overt maltreatment. A mixture of detrimental and beneficial effects was shown. In the 5CSRTT, attention was impaired in both genders, and in females, ELS increased compulsive-like behaviour. Novel object exploration was only increased by ELS in males, but the preference for novel spaces decreased in both genders. Baseline anxiety (EPM and ASR) and recognition memory were not affected. Unexpectedly, ELS decreased the ACTH response to novelty and swim stress and increased active coping in the FST in both genders. Cognitive impulsivity was decreased only in females, but impulsive action was not affected. The enhancement in maternal care may buffer the effects of ELS in a context-dependent manner.

Despite the development of valuable new techniques (i.e. genetics, neuroimage) for the study of the neurobiological substrate of psychiatric diseases, there are strong limitations in the information that can be gathered from human studies. It is thus critical to develop appropriate animal models of psychiatric diseases to characterize their putative biological bases and the development of new therapeutic strategies. The present review tries to offer a general perspective and several examples of how individual differences in animals can contribute to explain differential susceptibility to develop behavioural alterations, but also emphasizes methodological problems that can lead to inappropriate or over-simplistic interpretations. A critical analysis of the approaches currently used could contribute to obtain more reliable data and allow taking full advantage of new and sophisticated technologies. The discussion is mainly focused on anxiety-like and to a lower extent on depression-like behaviour in rodents.

Exposure of animals to footshocks (FS) in absence of any specific cue results in the development of fear to the compartment where shocks were given (contextual fear conditioning), and this is usually evaluated by time spent freezing. However, the extent to which contextual fear conditioning always develops when animals are exposed to other stressors is not known. In the present work we firstly demonstrated, using freezing, that exposure of adult rats to a single session of FS resulted in short-term and long-term contextual fear conditioning (freezing) that was paralleled by increased hypothalamic-pituitary-adrenal (HPA) activation. In contrast, using a similar design, no HPA or behavioural evidence for such conditioning was found after exposure to immobilization on boards (IMO), despite this stressor being of similar severity as FS on the basis of standard physiological measures of stress, including HPA activation. In a final experiment we directly compared the exposure to the two stressors in the same type of context and tested for the development of conditioning to the context and to a specific cue for IMO (the board). We observed the expected high levels of freezing and the conditioned HPA activation after FS, but not after IMO, regardless of the presence of the board during testing. Therefore, it can be concluded that development of fear conditioning to context or particular cues, as evaluated by either behavioural or endocrine measures, appears to be dependent on the nature of the aversive stimuli, likely to be related to biologically preparedness to establish specific associations.