Investigating the Effects of Mifepristone (RU486) in the Behavioral, Hormonal and Central Responses to Acute Stress

Depression is associated with glucocorticoid hypersecretion, due to dysfunction of the hypothalamo-pituitary-adrenocorticol axis (HPA-axis). Because excess glucocorticoids are associated with depressive-like features in humans, glucocorticoid receptor antagonists are currently being tested for antidepressant efficacy in clinical trials. In the current study the hypothesis that mifepristone (RU486), a glucocorticoid receptor antagonist, would decrease the neuroendocrine and central HPA-axis responses to an acute stressor and attentuate depressive like behavior in an animal model of behavioral helplessness (forced swim test) was tested. Adult male rats were treated with 10 mglkg RU486 (subcutaneous) for five days and then exposed to a IO-minute forced swim test (FST), conducted in Plexiglas cylinders. FST sessions were videotaped for later analysis of behavioral immobility. Plasma ACTH and corticosterone CORT were measured at 15min and 90min after FST cessation. Animals were perfused and brains were collected for immunocytochemical assessment of c-Fos expression in the medial prefrontal cortex (mPFC), a brain region implicated in both depression and central control of the HPA axis. RU486 significantly decreased peak ACTH and CORT concentrations following FST exposure. In addition, glucocorticoid negative feedback was at1enuated in RU486-treated animals exposed to the FST. Exposure to FST alone induced c-FOS expression in the mPFC, as measured by the number of c-Fos positive neurons. Treatment with RU486 significantly increased the number of rnPFC c-Fos positive cell following FST exposure. The behavioral data obtained from FST paradigm, demonstrated that RU486 decreased immobility in the FST illustrating the potential efficacy of this drug as an antidepressant. Collectively these data suggest that RU486 dampens HPA-axis responses to stress, possibly by enhancing the excitability of stress-inhibitory neurons in the mPFC. This is particularly exciting, given the fact that this neural region is associated with decreased neural activity during depression in humans.

The Effects of Eating Behaviors and Exercise Patterns on the Processing of Food and Exercise Related Stimuli

The effectiveness of Cognitive Behavioral Therapy (CBT) for eating disorders has established a link between cognitive processes and unhealthy eating behaviors. However, the relationship between individual differences in unhealthy eating behaviors that are not related to clinical eating disorders, such as overeating and restrained eating, and the processing of food related verbal stimuli remains undetermined. Furthermore, the cognitive processes that promote unhealthy and healthy exercise patterns remain virtually unexplored by previous research. The present study compared individual differences in attitudes and behaviors around eating and exercise to responses to food and exercise-related words using a Lexical Decision Task (LDT). Participants were recruited from Colby (n = 61) and the greater Waterville community (n = 16). The results indicate the following trends in the data: Individuals who scored high in “thin ideal” responded faster to food-related words than individuals with low “thin Ideal” scores did. Regarding the exercise-related data, individuals who engage in more “low intensity exercise” responded faster to exercise-related words than individuals who engage in less “low intensity exercise” did. These findings suggest that cognitive schemata about food and exercise might mediate individual’s eating and exercise patterns.