Genetic Selection For Coping Style Predicts Stressor Susceptibility

Genetically selected aggressive (SAL) and nonaggressive (LAL) male wild house-mice which show distinctly different coping styles, also display a differential regulation of the hypothalamic-pituitary-adrenal axis after exposure to an acute stressor. To test the hypothesis that coping style predicts stressor susceptibility, the present study examined line differences in response to a chronic stressor. Chronic psychosocial stress was evoked using two paradigms. In the first paradigm, a SAL or LAL male was living in sensory contact (except tactile contact) with a dominant SAL male for 25 days (sensory contact stress). In the second paradigm, a SAL or LAL male was, in addition to the first paradigm, defeated by a SAL male for 21 consecutive days (defeat stress). The sensory contact stressor induced in LAL mice chronic body weight loss and increased plasma adrenocorticotropic hormone levels compared to SAL mice and increased corticosterone levels, thymus involution and lower hippocampal mineralocorticoid receptor (MR) : glucocorticoid receptor (GR) ratio compared to LAL controls. The defeat stressor increased corticosterone secretion and caused adrenal hypertrophy and thymus involution in both mouse lines. Defeated LAL mice showed long-lasting body weight loss and higher corticosterone concentrations than SAL mice and lower hippocampal MR:GR ratio and decreased immobility behaviour in the forced swimming test than LAL controls. Hypothalamic corticotropin-releasing hormone mRNA expression was higher in defeated SAL than in controls. The present data show that both stress paradigms induced line-dependent physiological and neuroendocrine changes, but that the sensory contact stressor produced chronic stress symptoms in LAL mice only. This latter stress paradigm therefore seems promising to analyse the role of genetic factors in the individual differences in stress-related psychopathology.

Chronic Corticosterone Administration Dose-Dependently Modulates Aβ(1–42)- and NMDA-Induced Neurodegeneration in Rat Magnocellular Nucleus Basalis

The impact of glucocorticoids on β-amyloid(1–42) (Aβ(1–42)) and NMDA-induced neurodegeneration was investigated in vivo. Aβ(1–42) or NMDA was injected into the cholinergic magnocellular nucleus basalis in adrenalectomized (ADX) rats, ADX rats supplemented with 25%, 100%, 2×100% corticosterone pellets, or sham-ADX controls. Aβ(1–42)- or NMDA-induced damage of cholinergic nucleus basalis neurones was assessed by quantitative acetylcholinesterase histochemistry. Plasma concentrations of corticosterone and cholinergic fibre loss after Aβ(1–42) or NMDA injection showed a clear U-shaped dose–response relationship. ADX and subsequent loss of serum corticosterone potentiated both the Aβ(1–42) and NMDA-induced neurodegeneration. ADX+25% corticosterone resulted in a 10–90 nM plasma corticosterone concentration, which significantly attenuated the Aβ(1–42) and NMDA neurotoxicity. ADX+100% corticosterone (corticosterone concentrations of 110–270 nM) potently decreased both Aβ(1–42)- and NMDA-induced neurotoxic brain damage. In contrast, high corticosterone concentrations of 310–650 nM potentiated Aβ(1–42)- and NMDA-triggered neurodegeneration. In conclusion, chronic low or high corticosterone concentrations increase the vulnerability of cholinergic cells to neurotoxic insult, while slightly elevated corticosterone levels protect against neurotoxic injury. Enhanced neurotoxicity of NMDA in the presence of high concentrations of specific glucocorticoid receptor agonists suggests that the corticosterone effects are mediated by glucocorticoid receptors.

Chronic corticosterone administration dose-dependently modulates Abeta(1-42)- and NMDA-induced neurodegeneration in rat magnocellular nucleus basalis

The impact of glucocorticoids on beta-amyloid((1-42)) (A beta((1-42))) and NMDA-induced neurodegeneration was investigated in vivo. A beta((1-42)) or NMDA was injected into the cholinergic magnocellular nucleus basalis in adrenalectomized (ADX) rats, ADX rats supplemented with 25%, 100%, 2 x 100% corticosterone pellets, or sham-ADX controls. A beta((1-42))- or NMDA-induced damage of cholinergic nucleus basalis neurones was assessed by quantitative acetylcholinesterase histochemistry, Plasma concentrations of corticosterone and cholinergic fibre loss after A beta((1-42)) or NMDA injection showed a clear U-shaped dose-response relationship. ADX and subsequent loss of serum corticosterone potentiated both the A beta((1-42)) and NMDA-induced neurodegeneration. ADX + 25% corticosterone resulted in a 1.0-90 nM plasma corticosterone concentration, which significantly attenuated the A beta((1-42)) and NMDA neurotoxicity. ADX + 100% corticosterone (corticosterone concentrations of 110-270 nM) potently decreased both A beta((1-42))- and NMDA-induced neurotoxic brain damage, In contrast, high corticosterone concentrations of 310-650 nM potentiated A beta((1-42))- and NMDA-triggered neurodegeneration. In conclusion, chronic low or high corticosterone concentrations increase the vulnerability of cholinergic cells to neurotoxic insult, while slightly elevated corticosterone levels protect against neurotoxic injury. Enhanced neurotoxicity of NMDA in the presence of high concentrations of specific glucocorticoid receptor agonists suggests that the corticosterone effects are mediated by glucocorticoid receptors

Basal and stress-induced differences in HPA axis, 5-HT responsiveness, and hippocampal cell proliferation in two mouse lines

To characterize individual differences in neuroendocrine and neurochemical correlates of stress coping, two lines of wild house mice were studied. These mice are genetically selected for high and low aggression and show distinctly different behavioral strategies toward environmental stimuli. Long attack latency (LAL), low aggressive mice display a passive coping style, whereas short attack latency (SAL), high aggressive mice show an active coping style. It was hypothesized that this difference in behavioral coping style is associated with differences in stress system reactivity. This was tested by investigating the regulation of the hypothalamus-pituitary-adrenal (HPA) axis and the serotonin (5-HT) system and hippocampal cell proliferation rate in these mice under baseline and stress conditions. Baseline corticosterone output in LAL mice was found to be more sensitive to adrenocorticotropic hormone, but showed less day/night variation than in SAL mice. Furthermore, LAL mice showed lower hippocampal 5-HT1A receptor gene expression and function. Basal hippocampal cell proliferation rate was slightly lower in LAL than in SAL mice. Exposure to acute stress (forced swimming for 5 min) resulted in a hyper-reactive HPA response, a reduced increase in brain 5-HT metabolism, and an almost 50% reduction in hippocampal cell proliferation rate in LAL compared with SAL mice. Chronic psychosocial stress (sensory contact stress) induced long-lasting changes in the HPA axis in LAL, but not in SAL mice. In conclusion, these studies show that a genetic trait in behavioral coping style in wild house mice is associated with differences in HPA regulation, 5-HT neurotransmission, and hippocampal cell proliferation rate. The results further indicate that LAL mice have a higher stress responsivity than SAL mice. These results may have implications for a differential susceptibility for stress-related mood disorders

Long-term effects of social stress on brain and behavior: a focus on hippocampal functioning

In order to study mechanisms involved in the etiology of human affective disorders, there is an abundant use of various animal models. Next to genetic factors that predispose for psychopathologies, environmental stress is playing an important role in the etiology of these mental diseases. Since the majority of stress stimuli in humans that lead to psychopathology are of social nature, the study of consequences of social stress in experimental animal models is very valuable. The present review focuses on one of these models that uses the resident-intruder paradigm. In particular the long-lasting effects of social defeat in rats will be evaluated. Data from our laboratory on the consequences of social defeat on emotional behavior, stress responsivity and serotonergic functionality are presented. Furthermore, we will go into detail on hippocampal functioning in socially stressed rats. Very recent results show that there is a differential effect of a brief double social defeat and repetitive social defeat stress on dendritic remodeling in hippocampal CA3 neurons and that this has repercussions on hippocampal LTP and LTD. Both the structural and electrophysiological changes of principal neurons in the hippocampal formation after defeat are discussed as to their relationship with the maintenance in cognitive performance that was observed in socially stressed rats. The results are indicative of a large dynamic range in the adaptive plasticity of the brain, allowing the animals to adapt behaviorally to the previously occurred stressful situation with the progression of time

Long-term effects of social stress on brain and behavior: A focus on hippocampal functioning

In order to study mechanisms involved in the etiology of human affective disorders, there is an abundant use of various animal models. Next to genetic factors that predispose for psychopathologies, environmental stress is playing an important role in the etiology of these mental diseases. Since the majority of stress stimuli in humans that lead to psychopathology are of social nature, the study of consequences of social stress in experimental animal models is very valuable. The present review focuses on one of these models that uses the resident-intruder paradigm. In particular the long-lasting effects of social defeat in rats will be evaluated. Data from our laboratory on the consequences of social defeat on emotional behavior, stress responsivity and serotonergic functionality are presented. Furthermore, we will go into detail on hippocampal functioning in socially stressed rats. Very recent results show that there is a differential effect of a brief double social defeat and repetitive social defeat stress on dendritic remodeling in hippocampal CA3 neurons and that this has repercussions on hippocampal LTP and LTD. Both the structural and electrophysiological changes of principal neurons in the hippocampal formation after defeat are discussed as to their relationship with the maintenance in cognitive performance that was observed in socially stressed rats. The results are indicative of a large dynamic range in the adaptive plasticity of the brain, allowing the animals to adapt behaviorally to the previously occurred stressful situation with the progression of time. (C) 2004 Elsevier Ltd. All rights reserved