Date of Award

August 2021

Document Type


Degree Name

Doctor of Philosophy (PhD)


Genetics and Biochemistry

Committee Member

Trudy F.C. MacKay

Committee Member

Robert R.H. Anholt

Committee Member

Frank A. Feltus

Committee Member

Rajandeep Sekhon


Abuse and addiction to psychostimulants such as cocaine and methamphetamine present a worldwide health issue. Although the molecular mechanisms that mediate the effects of these drugs are well characterized, the underlying genetic basis of variation in differing responses to drugs of abuse are largely unknown. The Drosophila melanogaster model system can be used to identify genetic and transcriptional networks that underlie variation in effects of drug exposure that can serve as a blueprint for subsequent studies on humans. Drosophila possess a dopamine transporter to which cocaine and methamphetamine bind, and exhibit many of the effects that are observed in humans when cocaine and methamphetamine are consumed. Here, we use Drosophila to identify the underlying genetic and neurobiological factors that contribute to cocaine and methamphetamine use. Specifically, we identified genes and genetic networks with human orthologs that contribute to variation in consumption of and preference for cocaine and methamphetamine using genome-wide association analyses in the D. melanogaster Genetic Reference Panel (DGRP) and extreme QTL mapping in an advanced intercross population. Additionally, we performed single-cell RNA sequencing on brains of cocaine exposed flies and constructed genetic interaction networks from these data. Our results show that response to cocaine and methamphetamine in flies is genetically complex, sexually dimorphic, and involves multiple brain regions.



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