Involvement of the Orexin 1 and 2 Receptors in Nucleus Incertus (NI) on Modulation of Spatial Reference Memory in the Morris Water Maze.

Abstract

The nucleus incertus (NI) is a discrete region within the brainstem, situated in close proximity to the posterior aspect of the tegmentum. This region of the brain contains a diverse population of neurons that are involved in a range of functions, including stress response, arousal, learning, and modulation of the hippocampal theta rhythm. Additionally, orexin neuropeptides exhibit extensive distributions and overlapping actions within the NI. Nevertheless, the functions of orexin receptors within the NI remain poorly understood. The present study examined the effect of post-training and pre-probe intra-NI administration of SB-33486-A (OX1R antagonist) (12 μg/0.5 μl) and TCS-OX2-29 (OX2R antagonist) (10 μg/0.5 μl) on consolidation and retrieval in a Morris Water Maze (MWM) task. In Experiment 1, rats were trained in the Morris Water Maze (MWM) task and immediately after each training session received injections of dimethyl sulfoxide (DMSO) (control group), SB-334867-A, and TCS-OX2-29 into the nucleus incertus (NI). Experiment 2 was analogous to Experiment 1, with the exception that the rats received DMSO, SB-33486-A, and TCS-OX2-29 15 minutes prior to the probe test. In subsequent experiments, the probe and visible tests were conducted following the final training period, and the distance moved, escape latency, and velocity were recorded. In Experiment 3, rats that had undergone training in Experiments 1 and 2 were immediately subjected to trials for the assessment of visuomotor coordination on the visible platform. The results demonstrated that the spatial reference memory consolidation phase was markedly impaired by SB-334867-A or TCS-OX2-29 (P < 0.05), whereas the retrieval phase remained unaltered (P > 0.05). In light of these findings, it can be concluded that the orexinergic system in the NI plays a pivotal role in consolidation in rats through both OX1 and OX2 receptors.