BYU

Abstract by Alexandra Larson

Personal Infomation


Presenter's Name

Alexandra Larson

Degree Level

Undergraduate

Abstract Infomation


Department

Chemistry and Biochemistry

Faculty Advisor

David Michaelis

Title

Synthetic Process and Application of AP20187

Abstract

Drugs of abuse, including alcohol consumption, increase dopamine levels in the nucleus accumbens of the brain. This increase in dopamine levels is thought to underlie the rewarding aspects of these drugs and lead to addiction. The mechanisms, however, underlying alcohol's effects on dopamine release remain unclear. In this study, the Michaelis laboratory completed a total synthesis of a chemical dimerizer (AP20187). This molecule triggers cell death in macrophages expressing a specific protein. Transgenic mice using macrophage Fas-induced apoptosis (mafia mice) express this protein that recognizes AP20187, which enables selective depletion of macrophages in the brain. AP20187, was then used to study the role of the immune system in addiction. These studies, enabled by our synthesis, shed light on the mechanisms underlying alcohol’s effects on dopamine release in the brain. AP20187 allows us to better understand the mechanisms of addiction and potentially provide new strategies to address addiction in abused substances.