Alexander Thweni
Research Mentor(s): Jessica Anand
Mentor Department: Pharmacology
Authors: Alexander Thweni, Catherine Demery , Jason Witek, Peter Scott, John Traynor
Session: Session 3 (11:00am – 11:50am)
Presentation Type: Poster 47
Abstract
Opioid substance abuse is a critical public health concern, resulting in addiction and at times death. This project aims to design a PET tracer to map opioid receptors in the brain, determining the distribution of receptor density between chronic opioid users and non-users. The main objective is to create a molecule that binds tightly and selectively to the mu opioid receptor (MOR) without activating it while avoiding interaction with delta (DOR) or kappa (KOR) opioid receptors. Cell membrane fractions from cells overexpressing MOR, DOR, or KOR were used to test this hypothesis. The drugs tested underwent a serial dilution to establish how well the drug binds to the receptors at different concentrations. Radioactive GTPyS was used to measure receptor activation, and scintillation counting was used to measure how much of the drug bound to the receptors and how active the receptors were. These techniques allowed for precise data to determine the molecule’s binding affinity and receptor specificity. The molecule is expected to bind strongly and specifically to MOR without activating it, while showing little to no binding to DOR or KOR. These findings can prove its potential as a PET tracer for mapping MOR distribution in the brain. This study is a step forward in helping understand receptor adaptations in chronic and non-chromic opioid users, opening the door to new treatment options. By identifying differences in receptor density between users and non-users, the project helps address the opioid crisis through improved diagnostics and personalized treatment strategies.
