Do defects in synaptic plasticity underlie OCD-like Behaviors in a Novel Mouse Model?

Grant Type
Grant Year
Institution Location
Institution Organization Name
Duke University Medical Center
Investigators Name
Calakos, Nicole, MD, PhD

The symptoms of Obsessive Compulsive Disorder (OCD) are a common problem among patients and families with Tourette Syndrome. In general, neuro-psychiatric disorders are the toughest to model in animals because they involve problems with thought – something difficult to assess in an animal. In this project we will be using a newly created mouse strain that models OCD. Not only do these mice show many OCD-like features but, for the first time in an animal model, these symptoms have been treated with an OCD medication, fluoxetine (ProzacTM). Using this mouse strain, we will be testing the hypothesis that problems with synaptic plasticity may underlie some, or all, of the OCD-like behaviors in these animals. “Synaptic plasticity” refers to the ability of the connection between two nerve cells to change in strength in response to an experience and it is the mechanism by which we learn and adapt to experiences. Specifically, using our mouse model, we will test whether synaptic plasticity mechanisms are disrupted in the basal ganglia circuitry which is known to be important in both Tourette Syndrome and OCD. Positive findings could imply learning and adaptation problems at the cellular level in people with OCD and related disorders and may lead to a change in our thinking about the cause of these problems. This revised understanding could result in substantial changes on how we approach treating these disorders and lead to focus on new drug targets, cognitive therapy and other interventions that might affect basal ganglia synaptic plasticity. Nicole Calakos, M.D., Ph.D. Duke University Medical Center, Durham, NC Award: $75,000 This Award is funded by Ralph Ochsman and the Ochsman Foundation. Tourette Association of America Inc. – Research Grant Award 2008-2009