The opioid epidemic in the U.S. is a major public health crisis representing a massive societal burden. Approximately 65 million individuals are exposed to opioids annually, and a substantial proportion of patients go on to be diagnosed with opioid use disorder (OUD). Why are some people more susceptible to develop OUD? How can we improve preventative measures and available therapeutics to treat OUD?

In the Memory, Epigenetics, and Addiction Laboratory, we strive to better understand the neurobiology of OUD as well as the mechanisms underlying addiction vulnerability. Using a combination of rodent models of addiction and molecular biological approaches, Assistant Professor Mathieu Wimmer and his team aim to better understand the neural mechanisms contributing to OUD and to identify novel targets to ameliorate available pharmacotherapeutics to treat substance use disorders. 

It is well known that substance abuse is heritable and that genetic factors substantially contribute to addiction susceptibility. What about environmental factors such as parental history of opioid exposure? Mounting evidence suggests that parental life experiences can have profound and long-lasting consequences for future generations. These parental environmental factors can be transmitted to future generations via epigenetic mechanisms, which alter behavior or physiology without changing the DNA sequence. This question is especially relevant given the recent estimation that 5 million fathers meet the criteria for OUD in the U.S.

To study the effects of paternal opioid exposure on future generations, we have established multigenerational rodent models of addiction, where sires (fathers) learn to self-administer morphine and produce first-generation progeny. Our studies indicate that male offspring of morphine-exposed fathers are more susceptible to the reinforcing effects of opioids in adulthood. Moreover, first-generation progeny are also more sensitive to the pain-reducing properties of opioids. These findings highlight potential ways by which parental opioid exposure can shape sensitivity to opioids in future generations. Overall, our results have potential implications for pain and risk management of individuals with a parental history of opioid exposure. 

Substance use disorder is a lifelong, relapsing disorder with relapse rates on par with other chronic diseases like hypertension and asthma. Heightened drug craving during abstinence can trigger relapse and is a major barrier to recovery.

We use RNA sequencing, a technique that allows us to define gene expression changes caused by chronic opioid exposure in the brain. We intend to highlight long-lasting molecular alterations that contribute to increased and sustained drug craving long after drugs of abuse are no longer onboard.

Insight into these mechanisms can ultimately be used to reduce craving, prevent relapse, and promote long-term sobriety. The Memory, Epigenetics and Addiction Laboratory is part of an ongoing drug discovery effort to find new ways to improve treatments for substance use disorders.

Our progress is wholly attributable to the skills and collaboration of our lab members across many career stages, including undergraduate research assistants, PhD students, post-docs and laboratory technicians. We are deeply committed to increasing diversity in the scientific workforce. A major part of our lab mission is to provide an inclusive and supportive environment, where all lab members feel valued and are able to thrive. We believe a diverse workforce is critical for generating creative and innovative ideas to tackle complex questions. Check out our website for more information!