Depression is a devastating mental illness that robs many of ability to experience the tremendous joy of being alive. It is diagnosed by its symptoms, the most prevalent being a depressed mood. While we now have a basic understanding of the disease, all of the treatments available fall short in some category. In fact, some patients do not respond to any current medical treatment. The anesthetic ketamine, when administered at sub-anesthetic doses, exerts powerful and rapid antidepressant effects. These effects are often seen even when behavioral therapy or other antidepressants have failed. There has been a push in the research community to understand how ketamine exerts its antidepressant effects, in order to develop safer alternatives and understand the biological underpinnings of depression. This thesis identifies and characterizes a novel antidepressant effect of ketamine. Data presented here may clarify some controversies surrounding the literature on ketamine and, more importantly, lead to the development of novel, rapid-acting antidepressants.