The Modulatory Role of Orexin 1 Receptor in Nucleus Accumbens (NAc) on Spatial Memory in Rats

Neuropeptide orexin mainly exists in neurons within and around the lateral hypothalamus and exhibits high affinity to orexin 1 and 2 receptors (OX1R and OX2R, respectively). Orexinergic neurons send their axons to the nucleus accumbens (NAc), which expresses OX1Rs. Previous studies have shown the involvement of orexins and their role in learning and memory processes in the dorsal raphe nucleus and hippocampus. However, no study has examined the effects of orexins in the NAc on memory. The present study examined the effect of the post-training and pre-probe trial intra-NAc administration of SB-33486-A (OX1R antagonist, 12 μg/0.5μl) and TCS-OX2-29 (OX2R antagonist, 10 μg/0.5 μl) on the consolidation and retrieval of memory in the Morris Water Maze (MWM) task. In experiment 1, rats were trained in the MWM and, immediately after every training, received bilateral injections of dimethyl sulfoxide (DMSO) (control group), SB-334867-A (SB), and TCS-OX2-29 (TCS) into the NAc. Experiment 2 was similar to experiment 1, except that the rats received DMSO, SB, and TCS 15 min before the probe test. Probe and visible tests were performed after the last training, and the distance moved, escape latency, and velocity were recorded. In experiment 3, rats trained in experiments 1 and 2, immediately after the probe test, were given the trials for visuomotor coordination assessment on the visible platform. According to the results, the injection of SB increased the distance moved and escape latency in the treated groups, compared to the control group, in the consolidation phase of spatial memory (P<0.05) but not in its retrieval phase (P>0.05). However, TCS-OX2-29 had no effect. These results suggest that the inactivation of the NAc OX1Rs, but not OX2Rs, impairs the consolidation but not the retrieval of spatial memory in rats.