Events

Development and Characterization of Fluorescent Probes for Understanding Monoamine Neurotransmitter Pathways in the Brain

Presented By: Adriana Mendieta

Abstract:
The neuronal populations responsible for producing, delivering, and maintaining efficient chemical communication within the brain and central nervous system (CNS) play a vital role in regulating essential bodily functions through various neurotransmitters, including serotonin. Serotonin exists within a complicated system of X receptors, the most well-known of which is the 5ht2a receptor, which is increasingly researched due to its purported role in the psychedelic activity of drugs including LSD, psilocybin, and DMT. Despite this growing popularity, its precise localization remains unclear, largely because of the lack of tools capable of providing definitive identification. Current imaging methods for this receptor occur either with antibody labeling, fluorescent protein chimeras, or positron emission tomography; however, each method is rife with considerable drawbacks that make widespread investigation into unaltered tissue difficult. With the advent of a new age in psychedelic research, the development of small molecule fluorescent probes to study the localization of 5HT2A receptors in native systems is crucial for understanding their underlying mechanism of action in neuronal circuits of the prefrontal cortex (PFC). In addition to its canonical receptors, serotonin activity is also mediated by transporters, including the serotonin transporter (SERT), which belongs to the Uptake 1 class of monoamine transporters (MATs). A less studied class, Uptake 2 transporters, includes the organic cation transporters 1-3 (OCT1-3) and the plasma membrane monoamine transporter (PMAT). Appreciation for the significance of these transporters has grown and, with that, the need for developing tools for its study. Cell-based fluorometric assays have been developed for each transporter to elucidate whether a compound is an inhibitor or substrate. These assays were applied to several novel iboga alkaloids, derivatives of ibogaine, to explore the role of Uptake 2 in their complex pharmacology.