Early deprivation leads to altered behavioural, autonomic and endocrine responses to environmental challenge in adult Fischer rats

Abstract

Depression is diagnosed on the basis of abnormal positive affects (anhedonia) and negative affects (low mood, helplessness, coping deficit, fatigue), and associated physiological abnormalities include hyperactivity of the HPA endocrine system and autonomic nervous system. Adverse early life environments, including parent-offspring emotional and physical neglect, are associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Animal studies based on early life adversity can potentially yield environmental models of the developmental behavioural neurobiology of depression. In Wistar rats, we demonstrated that isolation of pups from dam and littermates at room temperature for 4 h per day on P1-14 (early deprivation, ED) led to adulthood anhedonia-like traits of reduced motivation to obtain gustatory reward and reduced social motivation, relative to subjects left undisturbed during infancy (non-handling, NH). We hypothesized that the depression-like effects of ED would be even more pronounced and multiple in the stress hyper-responsive Fischer rat strain. The effects of ED were studied relative to NH and 15 min of daily isolation (early handling, EH). Relative to NH and EH, which exhibited remarkably similar phenotypes, ED led, principally in males, to chronic traits of: reduced motivation for and consumption of gustatory reward; increased activity in the pre-test and test phases of the forced swim test; reduced coping behaviour in an aversive environment; attenuated plasma corticosterone stress response to a normal plasma ACTH stress response; increased hypertensive response to a novel environment; and increased prefrontal cortical serotonin. High sensitivity to an aversive early environment in male Fischer rats therefore constitutes an important model for the study of affective development and its neurobiology.

Baseline prepulse inhibition expression predicts the propensity of developing sensitization to the motor stimulant effects of amphetamine in C57BL/6 mice

“…This is opposite to the gradient commonly associated with rats (e.g., Verney et al 1985;PelegRaibstein et al 2006a;, although we have obtained a similar, yet non-significant, trend before in C57BL/6 mice (Bitanihirwe et al 2010). Hence, the possibility of a species difference might be likely, which may not be surprising given that a dorso-ventral gradient in hippocampal dopamine content is not consistent across rat strains (e.g., Rüedi-Bettschen et al 2006). This highlights the importance of replicating our current findings in other species and strains.…”

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…By contrast, early deprivation, early subjugation and peripubertal stressors lead to decreased HPA-axis activity in adulthood 35, 39, 64, 66 . The differences in the long term effects induced by the maternal separation and early deprivation models depend only on the social context of stress administration (that is, whether maternally separated animals remain with peers or isolated) 198 .…”

Animal models as tools to study the pathophysiology of depression

“…22,23 In contrast, treatment with antidepressants in animals deprived of maternal care was able to reverse depressive-type behaviors, promoting an increase in neurotrophin levels and neurogenesis. 2 …”