title: Developmental plasticity of HPA and fear responses in rats: a critical review of the maternal mediation hypothesis.
abstract: Developmental plasticity of HPA and fear responses in rats has been proposed to be mediated by environment-dependent variation in active maternal care. Here, we review this maternal mediation hypothesis based on the postnatal manipulation literature and on our own recent research in rats. We show that developmental plasticity of HPA and fear responses in rats cannot be explained by a linear single-factor model based on environment-dependent variation in active maternal care. However, by adding environmental stress as a second factor to the model, we were able to explain the variation in HPA and fear responses induced by postnatal manipulations. In this two-factor model, active maternal care and environmental stress (as induced, e.g., by long maternal separations or maternal food restriction) exert independent, yet opposing, effects on HPA reactivity and fearfulness in the offspring. This accounts well for the finding that completely safe and stable, as well as, highly stressful maternal environments result in high HPA reactivity and fearfulness compared to moderately challenging maternal environments. Furthermore, it suggests that the downregulation of the HPA system in response to stressful maternal environments could reflect adaptive developmental plasticity based on the increasing costs of high stress reactivity with increasingly stressful conditions. By contrast, high levels of environmental stress induced by environmental adversity might constrain such adaptive plasticity, resulting in non-adaptive or even pathological outcomes. Alternatively, however, developmental plasticity of HPA and fear responses in rats might be a function of maternal HPA activation (e.g., levels of circulating maternal glucocorticoid hormones). Thus, implying a U-shaped relationship between maternal HPA activation and HPA reactivity and fearfulness in the offspring, increasing maternal HPA activation with increasing environmental adversity would explain the effects of postnatal manipulations equally well. This raises the possibility that variation in active maternal care is an epiphenomenon, rather than a causal factor in developmental plasticity of HPA and fear responses in rats. Developmental plasticity of HPA and fear responses in rats and other animals has important implications for the design of animal experiments and for the well-being of experimental animals, both of which depend on the exact underlying mechanism(s). Importantly, however, more naturalistic approaches are needed to elucidate the adaptive significance of environment-dependent variation of HPA reactivity and fearfulness in view of discriminating between effects reflecting adaptive plasticity, phenotypic mismatch and pathological outcomes, respectively.
authors.affiliation: Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, National Institute of Health (ISS), Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Macrì
authors.forename: Hanno
authors.initials: H
authors.lastname: Würbel
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D004777:Environment; D005239:Fear / Q000502:physiology*; D005260:Female; D006234:Handling, Psychological; D006799:Housing, Animal; D007030:Hypothalamo-Hypophyseal System / Q000254:growth & development / Q000502:physiology*; D008297:Male; D008425:Maternal Behavior / Q000502:physiology*; D008426:Maternal Deprivation; D008960:Models, Psychological; D009473:Neuronal Plasticity / Q000502:physiology*; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology