John Mantsch, PhD

Dr. Mantsch joined the Medical College of Wisconsin (MCW) as the Chair of Pharmacology & Toxicology in January of 2021. Prior to his arrival at MCW, Dr. Mantsch served as the Chair of the Department of Biomedical Sciences at Marquette University, where he was a faculty member since 2001. Dr. Mantsch graduated from Allegheny College in 1993 with a BS in psychology and received his PhD in Pharmacology & Toxicology, with a specialization in neuropharmacology, from Louisiana State University Medical Center (now LSU Health) in Shreveport. He completed his post-doctoral training under Dr. Mary Jeanne Kreek in the Laboratory on the Biological of Addictive Disease at the Rockefeller University. Dr. Mantsch’s research program is focused on the neurobiology of stress, motivated behavior and addiction and has been continuously funded by the NIH since 2003. Dr. Mantsch has 20 years of pharmacology teaching experience and an extensive record of mentoring graduate students, undergraduate students, and post-doctoral trainees. He is involved in community health initiatives focused on mental health, health disparities, and substance use disorders through his translational research efforts, including his work with Promentis Pharmaceuticals, a company he co-founded which is now developing medications for neuropsychiatric diseases. Dr. Mantsch is the endowed Florence J. Williams Professor of Pharmacology and Toxicology at MCW.

Research Experience:

• Neuropharmacology
• Addiction/Substance Use Disorders
• Systems Neuroscience
• Neuroendocrinology
• Preclinical Models
• Stress
• Motivated Behavior

Stress and addiction are among the most pressing threats to health and wellness in modern society. Solutions to these challenges lie within the complexity of the brain. Recent advances in neuroscience have provided us with new tools, approaches and perspectives that should support meaningful progress in defining how the brain works. My laboratory seeks to leverage these advances to better understand and guide more effective interventions for stress-related disorders and addiction. There are several active lines of research in the lab, including those listed below:

Stress-induced relapse to drug seeking
The effective management of substance use disorders relies heavily on interventions aimed at relapse prevention. While there are many factors that determine relapse risk, stress is particularly problematic, as it is unavoidable, uncontrollable, and pervasive in the lives of those struggling with substance use disorders. Episodic stress can trigger craving in people and drug seeking in preclinical models. With the goal of guiding developing treatments aimed at minimizing the influence in substance use disorders, our work continues to define the neural pathways and mechanisms responsible for stress-induced cocaine seeking. The lab is also examining the mechanisms through which stress-triggered drug seeking is recruited/augmented with repeated excessive drug use and the underlying adaptations in neurocircuitry that mediates stress-related responses and motivation.

Influence of sex and stress hormones on drug-seeking behavior
Stress and sex hormones exert brain-wide effects to influence behavior at the network level. We have demonstrated that corticosterone administration, at a dose that reproduces stress levels in blood, and 17-beta estradiol, at dose that reproduces proestrus levels, promote cocaine seeking via rapid non-genomic mechanisms of action. Ongoing work in the laboratory is focused on understanding the brain regions and mechanisms that underlie the effects of these hormones on drug seeking. The implications of this work extend beyond substance use disorder and have the potential to advance our understanding of how stress and biological sex influence a range of healthy and pathological behaviors.

Impaired motivation in stress-related disorders
Chronic stress-induced dysfunction of the prefrontal cortex contributes to many stress-related disorders and is manifest, in part, as impaired motivation. We are currently exploring the mechanisms through which chronic stress produces functional and structural deficits in neural projections originating the prefrontal cortex that mediate motivated behavior with the goal of guiding the development of therapeutic interventions aimed at treating stress-related neuropsychiatric conditions, including depression.

The overdose crisis in Milwaukee County
We are in the midst of a drug epidemic, and overdose deaths are on the rise. Milwaukee has been hit particularly hard by this epidemic. Effective solutions require the identification of community-level factors that influence overdose risk and strong partnerships that support community-level responses. In collaboration with population health and data scientists and local partners we are working to understand the determinants of overdose risk (and other mental health-related challenges) with the objective of guiding policy and interventions that can promote community wellness.