Serotonin/ Dopamine Interactions in the Brain: Potential Revelance to Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale University
Investigators Name
Rasmusson, Ann, MD

Recent family-genetic studies suggest that vocal and motor tics, as well as obsessive-compulsive symptoms, are expressed in Tourette Syndrome. Biochemical and pharmacologic studies suggest that these symptoms are mediated in part by the serotonin and dopamine neurotransmitter systems. For instance, tics respond most reliably to pharmacologic blockade of the dopamine system, while obsessive-compulsive symptoms are most responsive to medications with primary effects on the serotonin system. A number of animal studies have demonstrated neuroanatomical, developmental, biochemical, and behavioral interactions between the dopamine and serotonin systems. It would thus be of interest to elucidate functional interactions between these two neurotransmitter systems in animal models of relevance to TS. I plan to do this using the new technique of intracerebral microdialysis. This technique will allow the continuous monitoring of serotonin and dopamine release in brain regions that have been implicated in recent positron emission tomographic (PET) studies of persons with Tourette Syndrome or obsessive-compulsive disorder. Since tics and obsessive-compulsive symptoms are exacerbated by stress and anxiety, I initially plan to characterize the patterns of dopamine and serotonin release in response to mild environmental stress or the pharnnacologic induction of anxiety. Subsequently, t will assess these patterns of neurotransmitter release after treatment with haloperidol and fluoxetine, medications used to treat tic and OCD symptoms. It has also been observed that many persons with TS who come to medical attention have symptoms of attention deficit and hyperactivity. Therefore, in the second phase of my research, I plan to investigate serotonin and dopamine release in the context of amphetamine-induced stereotypy and hyperactivity. Again I will study the patterns of neurotransmitter release before and after treatment with haloperidol and fluoxetine. The underlying neuropathology in Tourette Syndrome is still undefined. However, I hope that these studies will help clarify the relationship between the neurobiologic, behavioral, and pharrnacologic phenomenae observed in TS, as well as promote the development of more effective treatment strategies. Ann M. Rasmusson, M.D. Yale University, New Haven, CT Award:$20,000 Tourette Association of America Inc.. – Research Grant Award 1989