Project Type(s):
Basic Science

Fentanyl overdose is responsible for nearly 75,000 deaths each year in the U.S. and causes severe psychological, physical, financial, and social harm. Despite existing treatments, fentanyl addiction remains difficult to overcome due to the chronic and complex nature of fentanyl addiction which contributes to patterns of chronic use and high relapse rates. This is partly due to fentanyl’s ability to rewire the brain’s reward and executive cognitive system to cause lasting changes in mood and cognition while also triggering intense withdrawal symptoms that drive continued use. To better understand the widespread impact of fentanyl on the brain, this project uses mouse models of addiction to explore the effects of fentanyl on various brain regions and neural populations involved in reward, motivation, mood, and cognition. Using artificial intelligence-guided behavioral and cellular analyses, we then correlate these neural signatures to mouse behaviors during withdrawal and a cognitive working memory task. We will then test whether two promising emerging treatments, semaglutide and ketamine, can improve cognition, withdrawal symptoms, or mood in mice exposed to fentanyl. Through this, we will contribute to our understanding of how fentanyl exerts its negative effects which can inform the development of more effective therapies for its devastating impact.

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