Graduation Year

2024

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Neuroscience

Reader 1

Dr. Sandra Watson

Reader 2

Dr. Tessa Solomon-Lane

Rights Information

2023 Rachel M Corbett

Abstract

Studying the mechanisms of dopamine (DA) metabolism is critical to our understanding of neurological disorders such as depression, attention-deficit/hyperactivity disorder (ADHD), Schizophrenia, and Parkinson’s Disease and to the development of pharmacological treatments. The fruit fly serves as a useful model to study neurotransmitters such as dopamine and serotonin (5-HT) because they are highly conserved at the molecular and behavioral levels across the animal kingdom. A mutation in the drosophila dopamine transporter (dDAT), named fumin, exhibits hyperactivity due to increased postsynaptic DA signaling. Interestingly, administration of L-dopa, a precursor to DA, or amphetamine (AMPH), an illicit psychostimulant that increases DA, to fumin mutants results in a significant decrease in locomotor activity.

We hypothesize that this hypoactivity is due to either signaling at the DA autoreceptor, dD2R, or the false production and transmission of DA via 5-HT neurons, which utilize dopa decarboxylase (DDC), an enzyme that catalyzes the final step in DA and 5-HT production. To test these hypotheses, we employed drosophila activity monitors (DAMs) to track fly locomotor activity in different genetic and pharmacological backgrounds and analyzed this data using R. First, we established a dose-response curve of wild-type and fumin flies on control food and L-dopa food to determine the optimal dose to observe the hypoactive phenotype. Second, we knocked down dD2R specifically in DA neurons in fumin flies and administered L-dopa to determine whether hypoactivity persists. Lastly, we knocked down the DDC enzyme in 5-HT neurons to determine whether the enzymatic conversion of L-dopa to DA in 5-HT neurons leads to unexpected hypoactivity.

Preliminary data shows a significant decrease in daytime locomotor activity in the fumin flies with an inhibited DA D2-autoreceptor, suggesting the potential up-regulation of another DA uptake mechanism, which requires further investigation. This research has the potential to inform us of mechanisms for side effects related to L-dopa-based medications, the treatment of ADHD via DA and AMPH-based medications, and may provide a basis for future studies regarding the potential of 5-HT neurons to release DA at the synapse.

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This thesis is restricted to the Claremont Colleges current faculty, students, and staff.

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