Does a single exposure to social defeat render rats more vulnerable to chemically induced colitis than brief inescapable foot-shocks?

All mammals are to different degrees exposed to stressors being physical or social, which may affect health and well-being. Stressful and traumatic situations have direct effects on immune responses that may alter susceptibility to developing somatic illnesses. In animal research, different types of stressors have been investigated in studying the effect on bowel disorders, some stressors being more or less of environmental origin. We aimed, therefore, to explore whether a more natural stressor would differ from a stressor of more unnatural characteristics on dextran sulphate sodium (DSS) induced colitis in adult rats. Specifically, whether social stress within a single social defeat (SD) paradigm would be a more potent stressor than brief inescapable foot-shocks (IFS) in causing elevated faecal granulocyte marker protein (GMP), and crypt- and inflammation scores in colonic tissue. Three groups of male Wistar rats were used; socially defeated rats; inescapable foot-shock rats; and comparison rats. Main findings showed no difference between the groups on GMP levels. However, there was a significant difference on inflammation and crypt scores for the distal part of colon, detected through histology, where socially defeated rats were more susceptible. A single SD seems to be more adverse than inescapable foot-shock on DSS induced colitis, but further studies are recommended to validate a broader range of different outcomes comparing two such different rodent stress models.publishedVersio

Consequences of social defeat stress for behaviour and sleep. Short-term and long-term assessments in rats

Social stressors play a major role in the pathogenesis of affective disorders like anxiety and depression. These disorders are associated with altered behaviour (i.e. locomotor activity, harm avoidance, startle response, anhedonia and sexual behaviour), sleep alterations and abnormalities in the stress response. The animal social defeat (SD) model is based on a natural conflict situation where a male intruder rat eventually subordinates itself to an unfamiliar territorial resident conspecific. The effects of defeat are studied in the intruder rat. The main purpose was to study the face validity of the SD model for affective disorders by investigating short-term and long-term consequences of single and/or double exposure to SD on behaviour and sleep in rats. In particular, the intention was to evaluate if SD could reproduce the alterations in locomotor activity, harm avoidance, startle response, anhedonia, sexual behaviour, stress responses and sleep parallel to those observed in patients with affective disorders. Social defeat induced low activity in the central sector of the open field (OF) (Paper I), indicating high harm avoidance which may reflect anxiety-like or depression-like behaviour. No short-term or long-term effects were seen on total locomotor activity in the OF (Papers I and II). Further, a lack of habituation to the OF across days was seen, which may reflect long-lasting heightened anxiety (Papers I and III). Overall, in the elevated plus maze (EPM) test, SD rats showed less total locomotor activity, less percentage time and less activity on the open arms, lasting up to 3 weeks after defeat (Paper II), possibly reflecting anxiety-like behaviours. High acoustic startle responses (ASR) were seen as a long-term effect of SD, probably reflecting an anxiety-like state (Paper II). A short-lasting reduced preference for sucrose was seen (Paper II), indicating an anhedonic state that may be interpreted as a transient anxiety-like symptom. Sexual behaviour was not affected (Paper I). As a group, SD rats did not show altered corticosterone responsiveness to OF exposure (Paper III). The SD rats showed a short-term increase in duration of slow wave sleep (SWS) 2 and sleep fragmentation (Paper I). Overall, SD rats did not show long-term effects on sleep or EEG power (Paper III). The effects of SD on sleep may be interpreted as anxiety, because they were short-lasting and the common sleep alterations seen in depression were not induced (e.g. reduced SWS2 and REM sleep alterations). A secondary aim was to compare effects of SD to the effects of inescapable footshock (IFS) (Paper II). The two stressors induced a similar short-term effect on sucrose preference and similar long-term anxiety-like behaviours in the EPM test. Contrary to what was expected, SD rats showed the highest ASR, while IFS rats showed the lowest total activity in the OF test. The results may reflect fundamental differences between SD and IFS. Another secondary aim was to explore the relationship between levels of corticosterone prior to SD or IFS stressor, and the different post-stressor behaviours (Paper II). Low pre-stress corticosterone level was expected to be associated with anxiety-like behaviours following stress. Overall, such a relationship was not found. Contrary to what was expected, the SD rats with high pre-stressor corticosterone level showed the greatest ASR, while IFS rats with low pre-stress corticosterone level did not show alterations in ASR. This further supports differences between the SD and the IFS stressor. The final secondary aim was to investigate differences in effects of SD on behaviour and sleep in two subgroups of rats with different coping styles in the SD (Paper III). Contrary to what was expected, rats fighting back in the SD confrontation showed longer latency to leave the start box, and spent less time in the OF arena compared to those not fighting back, indicating anxiety-like behaviour. They also showed more fragmentation of sleep in SWS1 and SWS2. The results may suggest that rapid submission during SD may be more adaptive than surrender after a longer fight, given these outcome measures. In conclusion, the studies presented in this thesis show that exposure to SD induced both short-term and long-term consequences for multiple behavioural features and at least short-term consequences for sleep. The behavioural consequences of SD are different from those of IFS. The studies generally support a high degree of face value for the SD model as a model for affective disorders, more relevant to anxiety than to depression

Comparison of commercial ELISA assays for quantification of corticosterone in serum

Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify corticosterone levels for the assessment of stress in laboratory animals. The aim of this experiment was simply to evaluate if four different and widely used commercial ELISA assays would yield the same or similar values of corticosterone in serum samples taken from laboratory rats after the mild stress of being held for sampling blood from the saphenous vein. Trunk blood was sampled from 32 male Wistar rats 30 minutes after this mild stress exposure and analysed with each of four commercial ELISA kits. Both the Arbor Assays and the DRG-4164 kits were significantly higher than the DRG-5186 and the Enzo kits. There were no significant differences between the DRG-5186 and Enzo kits. Overall the correlations between kits were high. In conclusion, the commercial ELISA kits tested in the present experiment yielded different values of total corticosterone in the same serum samples. The precision in determining true values of the corticosterone level is low for these commercial ELISA kits, although they may be used to determine relative differences within studies

Does a single exposure to social defeat render rats more vulnerable to chemically induced colitis than brief inescapable foot-shocks?

All mammals are to different degrees exposed to stressors being physical or social, which may affect health and well-being. Stressful and traumatic situations have direct effects on immune responses that may alter susceptibility to developing somatic illnesses. In animal research, different types of stressors have been investigated in studying the effect on bowel disorders, some stressors being more or less of environmental origin. We aimed, therefore, to explore whether a more natural stressor would differ from a stressor of more unnatural characteristics on dextran sulphate sodium (DSS) induced colitis in adult rats. Specifically, whether social stress within a single social defeat (SD) paradigm would be a more potent stressor than brief inescapable foot-shocks (IFS) in causing elevated faecal granulocyte marker protein (GMP), and crypt- and inflammation scores in colonic tissue. Three groups of male Wistar rats were used; socially defeated rats; inescapable foot-shock rats; and comparison rats. Main findings showed no difference between the groups on GMP levels. However, there was a significant difference on inflammation and crypt scores for the distal part of colon, detected through histology, where socially defeated rats were more susceptible. A single SD seems to be more adverse than inescapable foot-shock on DSS induced colitis, but further studies are recommended to validate a broader range of different outcomes comparing two such different rodent stress models

Does a single exposure to social defeat render rats more vulnerable to chemically induced colitis than brief inescapable foot-shocks?

All mammals are to different degrees exposed to stressors being physical or social, which may affect health and well-being. Stressful and traumatic situations have direct effects on immune responses that may alter susceptibility to developing somatic illnesses. In animal research, different types of stressors have been investigated in studying the effect on bowel disorders, some stressors being more or less of environmental origin. We aimed, therefore, to explore whether a more natural stressor would differ from a stressor of more unnatural characteristics on dextran sulphate sodium (DSS) induced colitis in adult rats. Specifically, whether social stress within a single social defeat (SD) paradigm would be a more potent stressor than brief inescapable foot-shocks (IFS) in causing elevated faecal granulocyte marker protein (GMP), and crypt- and inflammation scores in colonic tissue. Three groups of male Wistar rats were used; socially defeated rats; inescapable foot-shock rats; and comparison rats. Main findings showed no difference between the groups on GMP levels. However, there was a significant difference on inflammation and crypt scores for the distal part of colon, detected through histology, where socially defeated rats were more susceptible. A single SD seems to be more adverse than inescapable foot-shock on DSS induced colitis, but further studies are recommended to validate a broader range of different outcomes comparing two such different rodent stress models