The university’s $8M NIDA grant will fund studies further exploring genetic factors leading to addiction onset.
The University of California San Diego School of Medicine recently secured an $8 million research grant from the National Institute on Drug Abuse (NIDA) to explore the genetics behind substance use disorders (SUDs). This five-year project is a major step in understanding why certain individuals are more prone to addiction than others. By uncovering the genetic factors that might lead to the onset of addiction, scientists hope to eventually develop personalized, effective treatments for SUDs, which remain a widespread public health concern impacting millions of Americans and burdening both the economy and healthcare systems.
Led by Dr. Abraham Palmer, a professor in the Department of Psychiatry, the team hopes to better understand genetic factors behind why some individuals who experiment with drugs or alcohol go on to develop addictive behaviors, while most do not. Palmer explains that genetic differences play a substantial role in this susceptibility, sparking questions about which chemical and cell variations that contribute to a higher risk of addiction. The team plans to use heterogeneous stock (HS) rats, a group known for its varied genetic backgrounds and individual responses to drugs, which closely resemble human reactions while engaging in addictive behaviors.
The research grant project builds on more than a decade of foundational research supported by NIDA. This long-term effort has allowed scientists to create a comprehensive database detailing both the genetic traits and behavior patterns of these HS rats, including their responses to addictive substances. This database provides a foundation for understanding which genetic traits are linked to specific behaviors, opening doors to more accurate therapeutic targets. One focus of this research is the amygdala, a brain region central to emotional regulation and addiction. Using single-nucleus RNA sequencing, Palmer’s team will expand upon previous research grant projects, comparing brain cells in the amygdala of rats that consumed high levels of cocaine with those that abstained.
Key findings have revealed that brain cells of cocaine-seeking rats showed increased oxidative stress, a condition where cells produce an excess of damaging reactive oxygen species. This stress affects cellular energy production, potentially changing how the brain interprets motivation and reward.
A particularly interesting discovery involves a gene known as Glyoxalase 1 (Glo1), which regulates oxidative stress and cellular metabolism. By blocking Glo1 activity with a compound called pBBG, researchers were able to reduce cocaine consumption in rats predisposed to addiction while leaving non-addicted rats unaffected. This result suggests that targeting Glo1 could help develop drugs that address addiction on a genetic level, potentially lowering relapse rates for people struggling with SUDs. Although Glo1 is a promising target, it’s only one piece of a larger genetic puzzle, with the project examining numerous other genes as possible keys to tackling addiction.
The findings from this study may extend beyond substance use disorders, offering insights into the genetic factors associated with other psychiatric conditions as well. By establishing a specific framework for understanding addiction, the team hopes to shift the focus of treatment from generalized to tailored therapies, improving outcomes for those most vulnerable to addiction.
Sources:
UC San Diego Awarded $8 Million to Uncover Genetic Foundations of Substance Use Disorders
UC San Diego receives $8 million grant to study the genetics of substance use disorder
UCSD School of Medicine Awarded $8 Million to Understand Genetic Foundations of Addiction
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