Date of Defense





The role of the orexin system in the neural mechanisms involved in reward processing and addiction is a recent area of scientific interest. Orexins (Hypocretins) are neuropeptide transmitters localized in the lateral hypothalamus. The orexin system has neuronal projections similar to the dopaminergic circuitry implicated in reward mechanisms and psychostimulant drug actions. Recent investigations have suggested a bidirectional modulation of the dopamine and orexin systems. This study examined the behavioral effects of orexin-A utilizingconditioned place preference (CPP) procedures. Twenty-fourmale Sprague-Dawley rats were stereotaxically implanted with bilateral guide cannulae into the peduncular lateral hypothalamus (PLH). Following recovery from surgery, rats were randomly assigned to one of three treatment groups (0, 250, or 500 ng). Immediately before conditioning trials, bilateral microinjections of orexin-A or artificial CSF were infused into the PLH at a rate of 0.5 ul/min. Using an unbiased design, each rat was placed into one side of the chamber following orexin-A injections and the opposite side of the chamber following aCSF injections. Locomotor activity was recorded over a series of six conditioning sessions, three with orexin-A and three with aCSF, administered in an alternating pattern over six consecutive days. On the test day, animals were allowed free exploration of the entire apparatus and locomotor activity and time spent in each side of the chamber were monitored and recorded. Results indicated that orexin-A produced significant and dose-dependent increases in locomotor activity. CPP test results indicated that both 250 ng and 500 ng produced a conditioned aversion to the orexin-A paired side of the chamber. These results are inconsistent with previous reports that lower doses of orexin-A produce rewarding effects.

Access Setting

Honors Thesis-Campus Only