Grant: Operating Grant

Dopamine is a natural chemical in the brain that carries signals between brain neurons. It is released by one set of neurons and attaches to special dopamine 'receptors' on another set of neurons. An abnormal increase in dopamine and number of receptors are thought to lead to schizophrenia. All current antipsychotic medications for schizophrenia seem to work through the dopamine D2 receptors. However, recent research has focused on the dopamine receptors called D3. Given that dopamine binds very tightly to the D3 receptors and these receptors are only localized to the brain regions which modulate emotions and motivation, small changes in the number or function of dopamine D3 receptors may lead to significant effects. Through brain imaging techniques like PET (Positron Emission Tomography), it is now possible to study the D3 receptors, measure their number and indirectly the amount of dopamine acting on them. The current study therefore seeks to quantify the amount of dopamine acting on the D3 receptors. To do this we will use a drug alpha-methyl-para-tyrosine (AMPT) to transiently decrease dopamine levels in order to "unmask" any D3 receptor - that is - available to be quantified using the PET imaging technique. We will compare these results in the same subject to the baseline state (i.e. "masked" state, in absence of AMPT). The difference between the D3 receptors, before and after the dopamine depletion, will provide a measure of the dopamine acting on these receptors. We will induce a decrease in the dopamine brain levels in 12 untreated patients with schizophrenia, and 12 healthy controls, matched to the patients in terms of age and sex. The results of this study may lead to a new diagnostic marker for schizophrenia, increase our understanding of the pathophysiology of the disease, and provide a new target for treatment.