The Carlezon lab is primarily interested in the biological basis and treatment of psychiatric illness, specifically nature/nurture issues as they relate to the brain and the basic processes by which the brain develops and is modified in response to experience. His Behavioral Genetics Laboratory, founded in 1998, aims to better understand how the environment affects behavior and the biology of the brain. “Environment” can mean many things, including exposure to stress, drugs, trauma, toxins, or illness. This work is relevant to many types of neuropsychiatric disorders, including depression, anxiety, PTSD, addiction, and autism.

Rather than trying to model neuropsychiatric conditions directly, Dr. Carlezon's lab uses multiple behavioral tests that capture their key signs, which in people are often overlapping (co-occurring). Ideally, the tests are sensitive to the same signs in animals that psychiatrists use to make diagnoses in people. We focus on the same types of endpoints in animals that can be collected and stored by smartphones, smartwatches, and activity trackers.

The work is performed in rats and mice using various strategies. For example, Dr. Carlezon and his staff might study how exposure to a particular type of stress affects motivated behavior, which is dysregulated in many types of neuropsychiatric disorders. They would then examine brain regions known to regulate motivation for the molecular changes that accompany observed behavioral changes.

To establish cause-effect relationships, genetic engineering techniques are used—for example, viral vectors and mutant mice—to reproduce individual molecular changes to see if they can cause the behavioral changes. Finally, this new information is used to design new medications that can block, reverse, or prevent the behavioral changes.

This strategy has been successful. Dr. Carlezon and his group were the first to report that a class of drugs called kappa-opioid receptor (KOR) antagonists has antidepressant, anti-anxiety, and anti-stress effects in their behavioral tests. These discoveries have led to considerable interest in KOR antagonists, which are now in advanced clinical trials for treatment-resistant depression. The lab works with other scientists at McLean and the Broad Institute to develop novel kappa antagonists, using techniques such as high-throughput screening and medicinal chemistry.