Examining p21 overexpression in the nucleus accumbens as a mediator of reduced cocaine self-administration in cocaine-sired rat

Mateo working at wet bench





Project Summary

This past summer, I worked in the Pierce Laboratory of Addiction Neuroscience under the mentorship of Dr. Sarah Swinford-Jackson and Dr. Christopher Pierce. The Pierce lab focuses on understanding the mechanisms underlying cocaine addiction, a problem affecting more than 2 million people in the United States. Previous studies have shown that parental cocaine taking significantly alters the epigenetic profile of offspring. One such study found that the male, but not female, offspring of cocaine-exposed sires exhibit a cocaine-resistance phenotype characterized by reduced cocaine intake compared to saline-sired controls. The male offspring also expressed higher levels of p21 in their nucleus accumbens (NAc), a brain region highly implicated in reward. My PURM project was focused on functionally validating whether the overexpression of the accumbal p21 mediated the cocaine-resistance phenotype. We hypothesized that overexpressing p21 in the NAc of drug-naïve rats would reduce cocaine self-administration relative to controls.

My primary role in the project was performing cocaine self-administration in rats which overexpressed p21 or a control fluorophore in the NAc, which was used to determine both total cocaine intake and motivation for cocaine. Following the cocaine-self administration, I validated that p21 was actually overexpressed in the NAc by using qPCR.

Through working on this project, I gained a much greater understanding of both the behavioral and molecular aspects of addiction neuroscience. On the behavioral side, I learned much more about when and why we would use different behavioral protocols, such as a progressive-ratio schedule, to analyze different things. On the molecular side, I learned many new techniques, such as isolating RNA and qPCR, which I am sure are invaluable to have as a student who is very interested in seeking to perform even more independent research in the future.

As a Biological Basis of Behavior major, I found every single topic I discussed with my mentors to be applicable to classes I had taken or planned to take in the future. Applying what I had learned in class to an actual lab setting helped me understand previously confusing topics as well as reinforce simpler ones. This truly was one of the most enriching summers of my life.