Temporal aspects of HPA axis reactivity and regulation: microdialysis studies in the HR/IR/LR mouse model

Abstract

Major depression (MD) is one of the most common affective disorders. Apart from vegetative and psychological symptoms, patients show profound neuroendocrine alterations often including a HPA axis dysregulation. In this study, a new animal model for affective disorders was used to elucidate the temporal aspects of HPA axis reactivity and feedback regulation. The so-called stress reactivity (SR) mouse model consists of three separate breeding lines – the high (HR), intermediate (IR) and low reactivity (LR) mouse line – with a significantly different reactivity of the HPA axis in response to stressors. In vivo microdialysis was used to monitor the increase of hippocampal corticosterone (CORT) concentrations after the onset of a stressor. Simultaneously, plasma CORT concentrations were measured via blood samplings. The experiments revealed: (i) distinct differences between the SR mouse lines regarding peak concentrations of CORT in the hippocampus and plasma (HR>IR>LR); (ii) all tested individuals showed this peak concentration around the same time point (45min) after the onset of the stressor, with HR mice showing the highest increase of hippocampal and plasma CORT concentrations; (iii) recordings of the circadian rhythm of CORT secretion showed a higher HPA axis activity in the HR mouse line. Thus, our findings suggest the SR model to be a promising tool for elucidating the molecular mechanisms of affective disorders and developing new treatment strategies for MD.