Orexins are excitatory neuropeptides that come in two isoforms, Orexin A and Orexin B, and serve as ligands for the G-protein coupled orexin 1 and orexin 2 receptors (Ox1R and Ox2R, respectively). Changes in orexinergic transmission are thought to contribute to attentional processing. While several studies have examined the role of Ox1Rs in attention, less research has assessed the contribution of Ox2Rs. Moreover, several lines of evidence suggest that the right medial prefrontal cortex is particularly critical for visual attentional performance. Taking all of this into consideration, the goal of the present experiment was to test the effects Ox2R blockade, via administration of TCS-OX2-29, in the left or right medial prefrontal cortex on visual attention. The results suggest that low dose administration of TCS-OX2-29 into the right, but not into the left, medial prefrontal cortex enhanced attentional performance. We speculate that relatively mild antagonism of Ox2Rs may have increased the sensitivity of these receptors to subsequent orexin transmission, thereby enhancing attentional performance. Ongoing projects in our laboratory are assessing whether these effects are observed when TCS-OX2-29 is infused into other brain regions known to be critical for attentional performance
