Advisory Committee Chair
Angela Carter
Advisory Committee Members
Aurelio Galli
Jennifer Deberry
Mark Bolding
Steven Rothenberg
William Tyler
Document Type
Thesis
Date of Award
1-1-2025
Degree Name by School
Master of Biomedical Engineering (MBE) School of Engineering
Abstract
Dopamine (DA) is a neurotransmitter involved in the regulation of essential behaviors, including motor control and reward processing. Alterations in DA levels can significantly modulate these behaviors: increased DA release is associated with heightened locomotion and enhanced preference for rewarding stimuli. Therefore, measuring behavioral changes in vivo provides critical insight into DA release and function. In this study, we quantified DA-associated behaviors by radiolytic stimulation of the Drosophila A-isoform of the transient receptor potential ankyrin type-1 A (dTRPA1(A)) channel and investigated how the human-immunodeficiency virus (HIV) and its secreted protein, the trans-activator of transcription regulatory protein (Tat), alter drug-induced behaviors. In Drosophila, dTRPA1(A) is an evolutionary conserved detector of noxious chemicals, and it is highly sensitive to reactive oxygen species (ROS) and hydrogen peroxide (H2O2). In biological systems, UV light and X-rays rapidly generate ROS and H2O2, triggering dTRPA1(A) activation. Radiolytic stimulation of the heat insensitive dTRPA1(A)10b isoform may provide a new method of non-invasive, deep-tissue control of genetically defined cells in mammalian models. Since our findings demonstrated that X-rays stimulated DA release, we further investigated X-ray-induced changes in DA-associated behaviors. HIV and amphetamine (AMPH) use disorder (AUD) is a complex bidirectional relationship, where AMPH use facilitates HIV transmission, and HIV infection has been linked to increased AMPH use. Although the underlying mechanisms supporting this disorder are unknown, Tat, a protein secreted by HIV infected cells, has been implicated in enhancing escalation of AMPH use. Tat has been shown to interact with the anionic lipid phosphatidylinositol 4,5-bisphosphate (PIP2), the key regulator in DA uptake and release by the human dopamine transporter (hDAT). Tat’s interaction with PIP2 may ultimately impair hDAT-mediated, AMPH-induced DA release and potentially drive increases in AMPH intake (escalation) to compensate for the reduction in rewarding stimuli. Thus, we sought to investigate Tat’s role in the regulation of AMPH-associated behaviors. To quantify DA-associated behaviors, we utilized DeepLabCut, a neural-network-based pose estimation program, and custom analysis code. We also developed a novel behavior assay incorporating a 3D-printed chamber to measure AMPH escalation and preference. This approach provides a quick and accurate framework for analyzing complex behaviors.
Recommended Citation
Goffinett, Hunter, "Stimulation And Quantification Of Dopamine-Associated Behaviors" (2025). All ETDs from UAB. 6839.
https://digitalcommons.library.uab.edu/etd-collection/6839
Comments
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