Date of Award:


Document Type:


Degree Name:

Doctor of Philosophy (PhD)



Committee Chair(s)

Timothy A. Shahan


Timothy A. Shahan


Mona C. Buhusi


Gregory J. Madden


Stephen J. Walsh


Katherine R. Brown


Depression is one of the most debilitating and widespread mental health conditions in the world today. Drugs that are traditionally prescribed to combat depression are flawed in several ways, and because of this, new treatments are needed. One drug that seems capable of overcoming the limitations of traditional antidepressants is ketamine. In clinical research, a single dose of ketamine can significantly reduce symptoms of depression quickly, its effects may last for weeks to months, and its side effects appear to be limited and relatively harmless. However, clinical research is ongoing, and more research is needed to fully understand ketamine's beneficial effects. One way that research can help understand how ketamine works is by using animal models of behavior. These models are beneficial because they allow researchers to isolate very specific variables that sometimes are not possible with human research. The specific approach used here is called reinforcement learning, which is well-suited to studying basic decision-making processes and how behavior changes based on receiving rewards and punishments. The experiment in Chapter 2 was designed to test the effects of different ketamine doses on behavioral adaptation, something that depressed individuals struggle with. Regardless of dose, ketamine did not enhance this ability, and instead appeared to cause short-lived impairments in healthy rats. The experiment in Chapter 3 was designed to assess the effects of ketamine on behavior when two different forms of negative outcomes were either combined or not. Ketamine again did not have any long-lasting effects, but rats showed enhanced behavioral adaptation and persistence when they experienced a combination of two negative outcomes. Together, these studies aimed to improve our understanding of what aspects of depression ketamine might be useful for, and how to improve upon future research using reinforcement learning procedures with non-human animals.