The Behavioral Effects of Glucocortoid Excess

A major component of the stress response is activation of the hypothalamic-pituitary-adrenal (HPA) axis which starts a cascade that culminates in glucocorticoid secretion from the adrenal cortex. Glucocorticoids increase the chance of survival in potential life-threatening situations. Excess glucocorticoid secretion in the response to a threat can have observable detrimental effects. Although the behavioral effects have not been extensively studied, the physiological effects of chronic stress can be induced in rats by artificially increasing their principle glucocorticoid, corticosterone. We hypothesize that chronically elevated corticosterone levels will increase anxiety-like behavior in rats. We will test this hypothesis by implanting subcutaneous pellets of corticosterone or cholesterol. After a specific recovery period, the rats will be put on an anxiety-provoking elevated plus maze (EPM) with two enclosed and two open arms. Rats have a tendency towards exploratory behavior, which in direct conflict with an inherent reluctance to enter open areas. The EPM exploits this conflict and has been validated experimentally to indicate that decreased open arm exploration is related to an increase of anxiety. The results of this experiment support the hypothesis which was shown by a reduced exploration of open arms on EPM by rats implanted with corticosterone pellets. By determining the behavioral effects of chronically elevated glucocorticoids, the neural mechanisms that mediate increased anxiety during glucocorticoid excess can be better understood. Future studies leading from this experiment include determining which specific parts of the brain are activated in response to stress.