Masters Degrees (Physiological Sciences)
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Browsing Masters Degrees (Physiological Sciences) by Author "Beselaar, Leandrie Corne"
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- ItemEstablishing and validating an unpredictable chronic mild stress rat model in a South African laboratory(Stellenbosch : Stellenbosch University, 2021-03) Beselaar, Leandrie Corne; Essop, M. Faadiel; Stellenbosch University. Faculty Science. Dept. of Physiology.ENGLISH ABSTRACT: There is growing concern regarding the societal implications of the increasing burden of chronic stress. In light of this, there are countless animal studies that are currently pursuing the underlying mechanisms of chronic stress-induced disease onset and/or evaluating therapeutic interventions. The unpredictable chronic mild stress (UCMS) model is widely used globally, however to the best of our knowledge it has not yet been employed in South Africa. The present study was therefore aimed at successfully establishing the UCMS model at Stellenbosch University, with the lesser goal of evaluating to which extent the validation tests succeed in confirming a chronically stressed state in the animals. Male Wistar rats (n=14) were subjected to a nine-week UCMS protocol. The rats were randomly exposed to one or more mild stressors per day and underwent a sucrose preference test (SPT) weekly, aimed at establishing levels of anhedonia. Additionally, detailed weekly monitoring was performed to observe aggressive behaviors and determine general well-being. Following the UCMS protocol, the rats underwent an elevated plus maze (EPM) test to establish the presence of anxiety-like behaviors, after which they were euthanized by decapitation. The results revealed distinct differences in individual responses to stress, therefore the Stress group was subdivided into Stress susceptible and Stress resilient groups, based on specific criteria. Despite no change in plasma corticosterone levels, molecular analyses showed that plasma adrenocorticotropic hormone levels were significantly increased in the Stress susceptible group. However, the sucrose preference of both Stress susceptible and Stress resilient groups increased over the experimental period. The EPM results revealed anxiety-like behaviors in the Stress susceptible rats, as they spent significantly more time in the closed arms of the EPM and made significantly less entries into open arms, compared to the Stress resilient group. We hypothesize that the Stress resilient rats have some protective mechanism against the effects of chronic stress. Another theory suggests that these rats are more resistant to such effects and take longer to experience the damaging effects thereof. The results of the behavioral tests used to validate the model showed that the EPM is a more robust validation of the UCMS model than the SPT. Overall, this study contributes to the existing theory that the UCMS model is difficult to establish across different laboratories. Although anxiety-like behaviors were observed in the Stress susceptible groups, the lack of plasma corticosterone changes and anhedonia in the same group suggests that the model might not have been entirely effective at creating a state of chronic stress. The study concludes that rodent models of chronic stress should be validated by multiple tests that focus on evaluating the animal as a whole and not just rely on a single behavioral or molecular parameter.