Characterizing the Role of the Lateral Orbitofrontal Cortex in Risky Decision Making and Drug Taking behavior

Abstract

Unnecessary risk-taking is a core characteristic of maladaptive behaviors such as addiction and gambling. Risk is defined as possible exposure to an unfavorable outcome which may include danger, loss, or harm. Engaging in risky behaviors despite the uncertainty of consequences alludes to the involvement of the prefrontal cortex as the region is vital for higher-order thinking and executive functioning. Adaptations or changes within the specific subregion of the PFC, known as the Orbitofrontal Cortex, are of particular interest due to a long history of literature supporting the idea that the region is heavily involved in Cocaine Use Disorder and decision making based upon past outcomes/value/risk. To investigate drug use despite negative consequences, a core trait of addiction, developed a punishment-based drug self- administration paradigm with intermittent access. I found that exciting the lateral OFC(lOFC) leads to animals both taking and seeking cocaine despite punishment. In another experiment, I found that inhibiting the region led to the animals being less likely to press the risky lever in a probability discounting paradigm. Together these two studies suggest the lOFC plays a role in various forms of risk-taking, with increased risk-taking correlated with higher regional activity and the opposite effect with less regional activity. From this information, I may be able to propose a possible target for future treatments.