Bryan Yamamoto

Digging in to the long-term consequences of in utero opioid exposure

Description of the video:

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Brady Atwood speaks in voiceover: I’m Brady Atwood and I’m an assistant professor in the department of pharmacology and toxicology at the Indiana University School of Medicine.
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Brady Atwood speaks in voiceover: My lab is very much interested in how drugs of abuse such as opioids affect how the brain functions.
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Brady Atwood speaks in voiceover: Specifically looking at how it changes the way brain cells talk to one another and how that translates into changes of behavior…
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Brady Atwood speaks in voiceover: with hopes of someday being able to find ways to undo some of those changes as ways to treat drug abuse and addiction.
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Brady Atwood speaks in voiceover: So we do have a project with the Grand Challenges Responding to the Addictions Crisis.
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Brady Atwood speaks in voiceover: Our project is very much focused on children that are born to mothers that were dependent on opioids or mothers that used opioids during pregnancy.
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Brady Atwood speaks in voiceover: Increasingly in the news, opioids have been abused for a long time, but there's anincreasing number of children that are born to opioid dependent mothers.
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Brady Atwood speaks in voiceover: And we don't quite know what the long-term outcomes for these children are.
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Brady Atwood speaks in voiceover: We don’t know how this will affect their ability to learn and develop and social interactions. 
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 Brady Atwood speaks in voiceover: We don't know how  this will affect gene expression and how that will affect their long term outcomes.
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Brady Atwood speaks in voiceover: The Addictions Grand Challenge was a fantastic opportunity. We brought together nine different investigators for our project with a range of expertise from understanding pharmacology, understanding genetics, physiology
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Brady Atwood speaks in voiceover: and we all got together and brought our different expertises and are approaching this project from a lot of different angles to really capture every aspect that we can of how this opioid overexposure affects children.
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A study by Indiana University School of Medicine researchers found in utero exposure in mice to methadone could negatively affect developmental milestones related to proper functioning of the sensory and motor systems in the brain. These findings could lead to new treatment options that reduce long-term damage to human babies from in utero exposure.

The opioid epidemic has had a tremendous impact on the U.S., resulting in thousands of deaths. While much has been studied about the long-term effect of substance use in adults, little is known about the long-term consequences of in utero exposure to opioids, including medication-assisted therapies, on health and risk for substance abuse later in life.

Co-led by Brady Atwood, Assistant Professor of Pharmacology and Toxicology at the IU School of Medicine, the study modeled the case of a woman dependent on the prescription opioid painkiller oxycodone who enters into a methadone maintenance therapy program and subsequently becomes pregnant, maintaining methadone use throughout pregnancy. The research team developed a model that resulted in mouse behaviors reminiscent of human opioid neonatal abstinence syndrome.

The research showed that methadone accumulates in the fetal brain and in the placenta, essentially bathing the brain in drug and producing developmental delays. The study is co-led by Bryan Yamamoto, Professor and Chair of the Department of Pharmacology and Toxicology, and is a part of IU’s Responding to the Addiction Crisis Grand Challenge.

"Our model replicated many of the features of human neonatal abstinence syndrome such hyperarousal, hyperthermia, and sudden twitching," Atwood said. "While we cannot make any specific clinical recommendations from what we observed in our mice, we can look at the biochemical changes we measured and then look for similar biomarkers in humans to see if they correlate. The key strength of an animal model is it enables us to conduct future research to determine the mechanisms whereby opioids impair development and by understanding those mechanisms, we can make predictions that can be tested in the clinic."

Atwood and his team also found that the immune system of mice prenatally exposed to methadone may be less active, which could influence susceptibility to infection, and that bone structure was altered, which may increase the probability of bone fracture. Prenatal exposure also altered the type of bacteria in the gut, which is increasingly known to influence body and brain function. Also, exposure may predispose the offspring to future alcohol abuse.

"The opioid epidemic has led to a growing number of babies being born to mothers that used opioid throughout pregnancy, but little is known of the biological mechanisms that underlie prenatal opioid exposure-induced long-term negative consequences," Atwood said. "Creating an animal model allowed us to explore those biological mechanisms with the aim of identifying novel treatment strategies for either harm reduction or therapeutic intervention."

Atwood and his team will use the model to explore the impact of other drugs and to test new therapies for treating both in-utero opioid exposure and neonatal abstinence syndrome.