The exposure of individuals with Tourette Syndrome (TS) to stress is known to worsen symptoms in individuals with the disorder. There is also evidence suggesting that neurons in the brain that utilize the compound dopamine (DA) as a messenger between neurons may be dysfunctional. Specifically, it has been hypothesized that DA neurons in the basal ganglia (an area involved in mediating movement), may be involved in the etiology of TS, although this hypothesis hasn’t been substantiated as yet. The lack of a good animal model for TS study has impeded research related to studying the etiology of TS. Indeed, an analogous animal model would allow one to conduct invasive experiments that could yield important neurochemical data about dopaminergic neurotransmission. Furthermore, the efficacy of various treatment modalities could be determined. Recently, we have discovered a genetically transmitted mutation in Zucker rats (stargazer rats) that produces a behavioral profile that may be analogous tC31C69C112o that observed in TS. For example, these animals show: 1) distinct head and neck tics; 2) extreme locomotor hyperactivity and stereotypy; 3) obsessive-compulsive behaviors such as circling and tail-chasing. All of the aforementioned behaviors show an early onset in these animals (14-21 days old) and their intensity is increased by stress. Furthermore, the behaviors disappear while the animals are asleep, and they are significantly reduced by the DA receptor antagonist haloperidol. Finally, as reported for TS in humans, the intensity of the tics decreases as the animals grow older. In this study a number of xperimental approaches will be used to examine the activity/function of dopaminergic neurons in the basal ganglia of the stargazer rats. These include receptor binding, microdialysis, immunohistocytochemistry and electrophysiology. Furthermore, the effects of various pharmacological agents on the behaviors will be examined. Clearly, we hope that this approach will yield new insights into the etiology and treatment of TS. Charles R. Ashby, Jr., Ph.D., St.John’sUniversity, Jamaica Award $24,000 Tourette Association of America Inc. – Research Grant Award 1996