The Role of High-affinity Dopaminergic Receptors in Tourette Syndrome Inhibition, An Endophenotype for Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Toronto Canada
Investigators Name
Strafella, Antonio, MD, PhD

Abnormalities of dopaminergic transmission play a key role in the pathogenesis Tourette syndrome (TS). We are proposing to study dopaminergic function in patients with TS (as compared to controls) using the radioligand [11-C]-(+)- PHNO during positron emission tomography (PET) to evaluate the high affinity, active form of the D2/D3 receptor density in the striatum and to compare it with the conventional D2/D3 receptor antagonist [11-C] raclopride, which binds to all dopaminergic receptors. By measuring the proportion of D2/D3 receptors in the active state, we may be able to obtain important insights into the disorder. In fact, only agonist radiotracers which bind preferentially to receptors in their high-affinity, active state, have the potential to differentiate between active and inactive state of receptors. Given the novelty of the proposed radiotracer, we anticipate that the results of this study will provide new insights into the pathophysiology of TS, and will suggest new avenues for investigation and treatment of the disorder. Antonio P. Strafella, M.D., Ph.D., Anthony E. Lang, M.D., Paul Sandor, M.D. University of Toronto, Toronto, Canada Award: $75,000 Commentary: Tourette syndrome (TS) is thought to be caused by an abnormality in a brain chemical called dopamine. Using a brain imaging technique called positron emission tomography (PET) the investigators will compare the activity level of dopamine receptors in different regions of the brain in adults, with and without TS. They anticipate that the results of this study will provide new insight into the biological basis of TS. This award is funded by Ralph Ochsman and the Ochsman Foundation Tourette Association of America Inc. – Research Grant Award 2011-2012