Wake-promoting effects of orexin: Its independent actions against the background of an impaired corticotropine-releasing hormone receptor system

It is widely accepted that orexin (hypocretin) bears wake-promoting effects. While under normal conditions the circadian rhythm of orexin release has a clear circadian distribution, the amplitude of orexin fluctuation is dampened in depression. Interestingly, clinical symptoms of depression include several sleep disturbances. In this disease, corticotropin-releasing hormone (CRH) seems to be another factor influencing sleep. As neurophysiological interactions and anatomical connections between the orexinergic and the CRH system point to mutual influences of these two neuropeptides, we examined whether a dysfunctional CRH-receptor system in two different CRH receptor knock out models alters general wake-promoting effects of orexin applied exogenously. Orexin was injected intracerebroventricularlly into CNS-restricted CRH-receptor type 1 knockout mice (CRH-R1 KO) and CRH-receptor type 2 knockout mice (CRH-R2 KO) and baseline sleep was recorded from the freely behaving mice. A third experiment included antisauvagine-30 injections (CRH-R2 antagonist) into CRH-R1 KO animals. Orexin had similar wake-promoting effects in CRH-R1 KO mice, in CRH-R2 KO animals and in CRH-R1 KO mice treated with antisauvagine-30. Consistent results were obtained from all corresponding control littermate experiments. According to our results we conclude that the wake-promoting effects of orexin are not influenced by a possible contribution of CRH. (C) 2011 Elsevier B.V. All rights reserved.