Abstract Epidemiological studies demonstrate that affective disorders are at least twice as common in women as in men, but surprisingly, very few preclinical studies have been conducted on female ...experimental animals. Therefore, the necessity of developing valid animal models for studying the pathophysiology of stress-related disorders in women is obvious. Chronic social stress has the potential to induce depression in humans and therefore we characterize here a chronic social instability stress paradigm in female rats. This consists of a 4-week period with alternating stressful social situations, including phases of isolation and crowding, in an unpredictable manner. At the physiological level, increased adrenal weight and plasma corticosterone levels indicated hyperactivity of the hypothalamus–pituitary–adrenal axis. Elevated plasma luteinizing hormone and disruption of the estrus cycle together with increased serum prolactin levels revealed disrupted regulation of the hypothalamus–pituitary–gonadal axis. Body temperature regulation was affected during the last week of stress such that stressed rats reduced their body temperature less during the rest phase than the controls, thus exhibiting a flattened temperature curve. Behaviorally, chronically stressed rats showed reduced sucrose preference and food intake. However, we did not observe any effect of stress on performance in the forced swim test and hippocampal neurotrophin levels were similarly unaffected. Our results indicate that, by using this social instability paradigm, female rats can be kept under chronic stress for weeks without habituation, and that ultimately the animals develop a depressive-like phenotype. This model may provide a valuable tool for further analyses of the neurobiology of stress-related disorders in women and has the potential to serve as a paradigm for screening novel antidepressant drugs with special efficacy in women.
With the steadily increasing number of publications in the field of stress research it has become evident that the conventional usage of the stress concept bears considerable problems. The use of the ...term 'stress' to conditions ranging from even the mildest challenging stimulation to severely aversive conditions, is in our view inappropriate. Review of the literature reveals that the physiological 'stress' response to appetitive, rewarding stimuli that are often not considered to be stressors can be as large as the response to negative stimuli. Analysis of the physiological response during exercise supports the view that the magnitude of the neuroendocrine response reflects the metabolic and physiological demands required for behavioural activity. We propose that the term 'stress' should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an organism, in particular situations that include unpredictability and uncontrollability. Physiologically, stress seems to be characterized by either the absence of an anticipatory response (unpredictable) or a reduced recovery (uncontrollable) of the neuroendocrine reaction. The consequences of this restricted definition for stress research and the interpretation of results in terms of the adaptive and/or maladaptive nature of the response are discussed.
To improve the spatial resolution and uniformity in modern high resolution brain PET systems over the entire field of view (FOV), it is necessary to archive the depth of interaction (DOI) information ...and correct for spatial resolution degradation. In this work we present the performance results of a high resolution LSO/GSO phoswich block detector with DOI capability. This detector design will be used in the new CTI High Resolution Research Tomograph, ECAT HRRT. The two crystal layers (19/spl times/19/spl times/7.5 mm/sup 3/) and a light guide are stacked on each other and mounted on a (2/spl times/2) PMT set, so that the corners of the phoswich are positioned over the PMT centers. The crystal phoswich is cut into an 8/spl times/8 matrix of discrete crystals. The separation of the LSO and the GSO layer by pulse shape discrimination allows discrete DOI information to be obtained. The high light output and the light guide design results in an accurate identification of the 128 single crystals per block. Flood source measurements document a very good homogeneity of events, energy centroid stability and energy resolution (14-20% FWHM) per single crystal. An intrinsic resolution of /spl sim/1.3 mm and the DOI feasibility is extracted by coincidence measurements with a single GSO crystal.
A measurement of the cosmic ray positron fraction e+/(e++e−) in the energy range of 1–30 GeV is presented. The measurement is based on data taken by the AMS-01 experiment during its 10 day Space ...Shuttle flight in June 1998. A proton background suppression on the order of 106 is reached by identifying converted bremsstrahlung photons emitted from positrons.
Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether ...neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and ≈ 80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience.
Stress, especially chronic stress, is one of the most important factors responsible for precipitation of affective disorders in humans. The animal models commonly used in the investigation of stress ...effects are based mainly on powerful physical stressors. In the majority of cases, these models are not relevant to situations that human beings encounter in everyday life. In our study, an animal model for chronic social stress has been developed for rats using a resident-intruder paradigm. This paradigm is considered a model of social defeat or subordination, and therefore may mimic situations occurring in humans. Rats were subjected daily to subordination stress for a period of five weeks and, in parallel, tested with a battery of behavioural tests. Chronically stressed rats showed behavioural changes, including decreased motility and exploratory activity, increased immobility in a forced swim test, and reduced preference for sweet sucrose solution (anhedonia). Reduced locomotor and exploratory activity represents a loss of interest in new stimulating situations, implying a deficit in motivation. Increased immobility in the forced swim test indicates behavioural despair, a characteristic of depressive disorders. Decreased sucrose preference may indicate desensitisation of the brain reward mechanism. Since anhedonia is one of the core symptoms of depression in humans, our findings suggest that the rat chronic social stress model may be an appropriate model for depressive disorders.
Stress can be a threat to the physiological and psychological integrity of an individual and may result in psychic and behavioral changes. The stress response is mediated through in-concert activity ...of many brain areas and there is experimental evidence that stress induces structural changes in neuronal networks, in particular in the hippocampus, the prefrontal cortex and the amygdala. Within the hippocampal formation, stress exposure results in remodeling of dendrites of the CA3 pyramidal neurons and in reduced numbers of synapses on these neurons. Furthermore, stress inhibits adult neurogenesis in the dentate gyrus and appears to modulate the GABAergic system. In the prefrontal cortex, repeated exposure to stress causes dendritic retraction and loss of spines in pyramidal neurons whereas in the amygdala stress can elicit dendritic hypertrophy. These microscopically detectable changes in neuronal structures indicate the reorganization of neuronal networks. Moreover, molecular studies show that stress modulates expression of genes involved in neuronal differentiation and/or structural remodeling. Since a wealth of data documents the adverse effects of stress on emotions and cognition these alterations are commonly interpreted as the deleterious effect of chronic stress on the central nervous system. However, it is also possible that at least part of these changes reflect adaptive responses, as the network system rearranges its connections in order to cope with the changing requirements from the internal or external environment.
Sustained stress can have numerous pathophysiological effects. Adrenal glucocorticoid hormones are principal effectors in the stress response. They have profound effects on mood and behavior and ...affect neurochemical transmission and neuroendocrine control. We have used the experimental paradigm of chronic psychosocial stress in tree shrews to investigate the impact of aversive social encounters on brain structures. Chronic stress in male tree shrews which is accompanied by constantly elevated levels of glucocorticoids leads to structural changes in hippocampal neurons. Whereas dendritic atrophy of hippocampal pyramidal neurons and impairment of neurogenesis in the dentate gyrus could be demonstrated in chronically stressed tree shrews, a loss of hippocampal neurons was not observed in this animal model. The present review summarizes recent results on the question which structural changes occur during chronic stress in neurons of the brain and whether glucocorticoids might be responsible for such stress effects. The role of transmitter systems in stress-related neuronal plasticity is also discussed.
PDF
