Drug-Induced Impulsivity: The Impact of the Selective Blockade of Dopamine and Norepinephrine

Project Title

Drug-Induced Impulsivity: The Impact of the Selective Blockade of Dopamine and Norepinephrine

Faculty Mentor(s)

Project Description

In 2023, 48.5 million people over the age of 12, met the criteria for a substance use disorder (www.samhsa.gov). Both men and women can get addicted to psychostimulants, like cocaine, but women tend to progress through the disease faster than men do (Becker and Koob, 2016; Towers et al., 2023). This effect is mirrored in rodent models (Towers et al., 2023). This rewarding effect was increased in female rodents in the proestrus stage of the rodent hormone cycle (Calipari et al., 2017). Impulsivity is a core feature of substance abuse (Lee et al., 2019). Both in humans and animals, a signature effect of psychostimulants is decreased impulse control (Paine et al., 2023); an effect that is potentiated in female rats. Cocaine increases synaptic levels of dopamine and norepinephrine by blocking the reuptake of these neurotransmitters. Notably, research shows dopamine increases impulsivity, while norepinephrine decreases impulsivity (offering a possible therapeutic effect) (Calipari et al., 2017; Mei et al., 2021; Mandela et al., 2006). These results have been seen in males across many studies, with females often neglected. The goal of my project is to determine if there are sex-differences in the selective blockade of dopamine and norepinephrine reuptake transporters. We will also assess if ovarian hormone cycling has an effect on these results. To do this we will use the Differential Reinforcement of Low Rates of Responding (DRL) task to measure impulsive action and determine if dopamine and norepinephrine reuptake transporter activity fluctuates across the estrous cycle. At the end of our experiment we will determine if there are sex differences in the expression of dopamine and norepinephrine transporters in relevant brain areas through western blot analysis.

Why is your research important?

Substance Use Disorder (SUD) is a fairly widespread condition and impacts many people and their families. There are two aspects of my research that serve different aspects of  (SUD). The first is that one of our priorities is understanding if there are sex differences in the way that impulsivity impacts drug use and where in the brain they occur. Second, dopamine is fairly understood in how it affects drug-induced impulsivity, but norepinephrine is not, I hope we’ll be able to see potential therapeutic effects. 

What does the process of doing your research look like?

On the day-to-day, we conduct behavioral data with the rats. This fall I’m working with Suzie Vo and Lindsey Chou to be able to do this seven days a week. When we’re not collecting behavioral data we’re performing western blot analysis on the brain areas associated with impulsivity.

In what ways have you showcased your research thus far?

I’ve worked with my honors committee to present my written honors proposal, as well as presenting at the Neuroscience Honors Lunch to Neuro faculty and students associated with the department. In Spring 2025, I’ll present my completed honors thesis to my committee, the Oberlin community and at the Oberlin College Undergraduate Research Symposium.

What is your favorite aspect of the research process?

My favorite aspect of the research process is getting to see the transition from behavior testing to computational analysis. I find it so impactful to see all sides of the research process from reading journal articles to collect background information, to seeing how behavior is impacted, and ultimately to seeing if the biological structures of the brain match the behavior observed. I really appreciate getting to participate in every aspect of the research process.

How has working with your mentor impacted the development of your research project? How has it impacted you as a researcher?

I’ve gotten to connect a lot with Professor Paine throughout the development of and throughout my honors project. Having a close relationship with my mentor has impacted me very positively. I think being so comfortable around her has made asking questions, big or small, and coming together to solve issues very easy.

How has the research you’ve conducted contributed to your professional or academic development?  

My project has cemented my interest in conducting research in the future. It’s fairly different from the lab work we do in class so I appreciate the opportunity to collaborate on a more extensive research project and get the chance to work on every step of the process.

What advice would you give to a younger student wanting to get involved in research in your field?

Take the lab courses with your lectures if you can so you can get a sense of what type of Neuroscience research you’re most interested in. Start talking to professors early and be persistent– you will learn a lot about your research interests as you go through Oberlin and maintaining contact with professors as you figure that out is important!