The modulation of the spatial reference memory by the orexinergic system of the dorsal raphe nucleus

The dorsal raphe nucleus (DRN) is a brainstem nucleus involved in the pathophysiology of the depression, through its serotoninergic innervation. Furthermore, depressive symptoms in patients are also associated with some memory and sleep complaints. Anatomical evidence confirmed the presence of projections from the lateral hypothalamus to serotonergic neurons of the dorsal raphe nucleus (DRN). These projection fibers release orexin neuropeptides which play roles in the spatial memory. Both of the orexinergic receptors are widely distributed in dorsal raphe nucleus. Therefore, the present work was aimed to assess the probable roles of orexin 1 and 2 receptors using an orexin 1 receptor antagonist, SB-334867-A, and an orexin 2 receptor antagonist, TCS-OX2-29 in the DRN on the retrieval, and consolidation phases of spatial reference memory in the Morris water maze (MWM) task. The results demonstrated that blocking orexin 1 receptors in the DRN impairs the process of memory consolidation in the spatial MWM via increasing in the time of the escape latency of the probe day. Blocking these receptors did not affect the retrieval phase of MWM learning. Furthermore, blocking of the orexin 2 receptors in this area did not affect neither consolidation nor retrieval phases of the memory. In conclusion, orexin 1 receptors in the DRN play major roles in the consolidation of the spatial reference memory in rats.