Depression has sleep disturbances as a key symptom and recently sleep has been suggested as a new area to optimize treatment in depression. Orexin is produced in the hypothalamus and projected throughout the brain innervating a number of structures important in depression. It controls a number of physiological processes including sleep, arousal, cognitive processes and stress, which are affected during depression.

The study examines the possible implications for abnormalities in the orexinergic system in depression. We aim to determine whether treatment targeting this system relieves depressive symptoms.

Using real-time qPCR and Western blotting optimal sampling time is determined by an assessment of the diurnal variation of orexin expression. Expression of orexin and its receptors are investigated in the hypothalamus, the hippocampus, and the prefrontal cortex of the Flinders Sensitive Line (FSL) and the Chronic Mild Stress model of depression. Behavioral and molecular response to treatment with a conventional antidepressant and an orexin receptor antagonist will be addressed in FSL rats. In addition, we will include exercise as a noninvasive treatment, which has shown positive effects on both sleep and depression in humans.

Real-time qPCR analysis showed increased expression of the orexin-1 receptor (40%) and the orexin-2 receptor (39%) in the prefrontal cortex of FSL rats compared to the control rats, the Flinders Resistant Line rats.

This study may provide a platform for screening of drugs with effects on both sleep and depressive symptoms with perspectives for the development of novel strategies for treatment of depression.