Preclinical Models

Kafui Dzirasa holding a small chip

The preclinical research in our department provides an essential mechanistic basis for understanding behavioral dysfunctions and the development of better treatments for mental illness.  

While our preclinical research portfolio is somewhat broad, special emphasis is placed on depression and anxiety, drug abuse, posttraumatic stress disorder, cognitive dysfunction and the preclinical testing of compounds to treat various neuropsychiatric conditions that can lead to clinical trials in patients.  

Mouse genetic and rat models are used to probe genetic, epigenetic, molecular, biochemical and cellular mechanisms that underlie various neuropsychiatric-like illnesses and this information is used in conjunction with ongoing clinical studies in the department to provide a more comprehensive perspective on mental disorders.

Dr. Kafui Dzirasa’s lab studies the encoding of emotional behaviors in mice. His lab uses neuroengineering as well as artificial intelligence and machine learning approaches to study the neural dynamics underlying emotional states, how they are modified with psychiatric illnesses, and how they can be returned to their initial homeostatic conditions. They also aim to develop new devices to repair brain circuits in individuals suffering from devastating psychiatric illnesses. Watch this video or visit Dr. Dzirasa's lab website to learn more.

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Dr. Edward D. Levin’s lab investigates the neurobehavioral effects of drug abuse and environmental toxicants on rats and zebrafish. The research on nicotine, opiates, alcohol, cannabinoids and stimulants have revealed a variety of pharmacological treatments for clinical development. The environmental toxicology research has focused on the roles that pesticides, heavy metals and persistent organic pollutant exposure exert on neurobehavioral development, with special emphasis on cognitive and emotional dysfunction. This research has produced results that have impacted the federal regulation of pesticide use and treatments against neurotoxic damage.  

Related: An article co-authored by Dr. Levin was named 2023 Toxicological Sciences Paper of the Year! Learn more

Dr. Chris Marx’s lab conducts translational research investigating neurosteroids and other small molecules as biomarkers and new therapeutics for traumatic brain injury, post-traumatic stress disorder, pain, schizophrenia, and Gulf War Illness. Projects span biomarker studies in rodent models, postmortem brain tissue and clinical cohorts, in addition to proof-of-concept randomized controlled trials.  

The lab uses state-of-the-art mass spectrometry-based approaches to quantify neurosteroids with attomolar sensitivity, providing a cornerstone for translational projects interrogating the biomarker potential of neurosteroids and testing their therapeutic promise in Phase II clinical trials and neuroimaging investigations to accelerate the development of new pharmacological interventions.

Dr. Scott D. Moore’s lab examines how acute and chronic intermittent ethanol exposure affect neuropeptide responses using a combination of genetic and electrophysiological strategies in rodents. In addition, his lab is using a transgenic mouse model of age-dependent deficits in synaptic integrity (analogous to neurodegenerative disease in humans) in combination with electrophysiological, biochemical and behavioral approaches to analyze brain circuit alterations following acute head injury.

Dr. Scott Swartzwelder’s lab analyzes how rodent adolescent alcohol exposure compromises brain and behavioral functions in adulthood through interacting epigenetic, neuroinflammatory, neuronal and glial mechanisms. His lab has found that some of these effects are reversible with pharmacological treatments in current clinical use.

This work is being extended to human subjects, where the disparate ethanol drinking patterns among minority and multi-minority individuals of college age are examined. In addition, the lab is studying the transgenerational effects of rodent paternal cannabinoid exposure on neural and behavioral functions of the offspring in adulthood. 

Dr. William C. Wetsel's lab is studying the effects of psychedelics and various compounds that have biased signaling at G protein coupled receptors. Dr. Wetsel, the director of Duke’s Mouse Behavioral and Neuroendocrine Analysis Core Facility, has identified and investigated many different mouse genetic models of neuropsychiatric illness including autism, attention deficit-hyperactivity disorder, anxiety, depression, obsessive-compulsive disorder, schizophrenia, bipolar disorder, drug abuse, frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer’s disease and Parkinson’s disease.  

Dr. Douglas E. Williamson’s lab conducts translational epidemiologic studies on stress disorders including depression and PTSD. Using a variety of clinical, epidemiologic, human postmortem and preclinical study designs, the lab has identified unique gene signatures for PTSD, especially in the prefrontal cortex. These findings in humans are being extended to mouse models where changes in gene enrichment in the prefrontal cortex are evident immediately after exposure to a traumatic event. Whole genome in situ RNA sequencing is being used to identify the location of these transcription signals and their local networks in human and rodent brain.