Depression is a very common psychiatric disorder affecting approximately 20% of the general population at least once in their life. The prevalence is twice as high in women as in men. Although there are several hypotheses for the underlying neurobiology and pathophysiology, the neural underpinnings of depression remain incompletely understood. One of the most widely accepted concepts relates to the role of chronic stress as a precipitating factor for the development of depression. In accordance with the “stress theory of depression” it has been shown that patients with Cushings syndrome, and therefore very high glucocorticoid levels, show depressive symptoms. Stress also impairs synaptic signalling and neuronal plasticity in several brain regions forming part of the neural circuitry of depression. Several rodent models based upon the stress hypothesis exist with the aim to induce depression-like behaviour in laboratory animals and to examine the consequences of novel antidepressant treatment approaches.
The present study aimed at comparing two published protocols for the induction of depression-like behaviour in mice based upon chronic oral glucocorticoid application. Given the gender distribution in the prevalence of depression, the second goal of this study was to reveal possible differences in the behavioural and endocrine responses of female and male mice to corticosterone treatment. CORT treatment was found to alter circulating glucocorticoid levels and to modulate depression-like behaviour in selected behavioural paradigms in a sex- and protocol-specific manner. These data need to be considered for the experimental design and interpretation of future studies in the field and further suggest the high individual variability to be considered as relevant parameter for the statistical and experimental planning.