Abstract: The Effects of Medial Prefrontal Cortical Administration of an Orexin-1-Receptor Antagonist on Attentional Performance in Rats

The brain is undoubtedly the most complex organ in our body. Decades of research have been dedicated to unraveling neural circuitry. In the field of neuroscience, the complete understanding of neural pathways and how they contribute to various cognitive functions requires a comprehensive investigation of the specific components involved. This project will explore key components of a neural pathway related to attentional processing. Deficits in attentional processing occur in many neurological disorders, and understanding the pathways involved can provide implications towards new therapeutic targets.

This summer, I’ll be working in Professor Burk’s lab to investigate the effects of medial prefrontal cortical administration of the orexin-1-receptor antagonist, SB-334867, on attentional performance in rats. The medial prefrontal cortex (mPFC)—the target for this study’s drug—is important for executive functions, including the processing of different sources of information. The orexin system, involving neurons that project to numerous regions of the brain, plays a role in various attentional and physiological processes. Orexinergic transmission involves the release of excitatory neuropeptides (orexin A and orexin B) that bind to two receptors, orexin 1 and orexin 2. In general, orexin receptor antagonists disrupt attentional performance. An honors thesis study done by a student in Professor Burk’s lab last year, however, revealed some unprecedented results when looking at transmission through the mPFC. He found that low dose administration of an antagonist drug that targets the orexin-2-receptor in the mPFC actually enhanced attentional performance, while higher doses disrupted attentional performance, as predicted. These findings suggest that mild antagonism of the orexin receptors may actually increase receptor sensitivity for the subsequent transmission of orexins, thereby enhancing attentional performance. My project will investigate whether the same effects are seen in the orexin-1-receptor.

This study will hopefully elucidate some of the complexity underlying orexinergic transmission. A clearer understanding of the orexin system may lead to the development of novel treatments for Alzheimer’s Disease, schizophrenia, narcolepsy, and other pathologies characterized by attentional dysfunction.