Central nervous system stimulants are widely used in the treatment of behavioral disturbances in children such as attention deficit disorder (ADD). Stimulant drug treatment decreases hyperactivity and improves the attention span of children diagnosed as having ADD. While stimulant drug therapy is used in the treatment of ADD, there may also be side effects whose symptoms resemble those of Gilles de la Tourette Syndrome. The stimulants used in ADD therapy, such as methylphenidate, are known to act upon brain cells which contain the neurotransmitter dopamine. It is believed that dopamine may also be involved in the etiology and pathogenesis of Tourette Syndrome. Successful treatment of patients exhibiting Tourette Syndrome with dopamine blocking agents suggests that the disease may arise from a hyperactive dopaminergic system. The mechanism of stimulant drug-induced symptoms of Tourette Syndrome is not clear. It would be useful to characterize the interaction of such drugs (i.e. methylphenidate) with dopamine cells. We propose to do this by utilizing a three-dimensional reaggregate tissue culture system in which the sensitivity of central dopamine cells of pharmacological agents can be assessed. In this system fetal tissue from embryonic mouse brain is dissected, dissociated into single cells and then placed into rotator culture. Thus, developing embryonic and neonatal dopamine cells can be exposed to known concentrations of drugs over extended periods of time. We hope that the examination of the effect of methylphenidate on dopamine cells in reaggregate tissue culture will yield some insights into causes of the naturally occurring Tourette Syndrome. Alfred Heller, Ph.D., M.D., Department of Pharmacological and Physiological Sciences The University of Chicago, Chicago, IL Award: $25,000 Tourette Association of America Inc. – Research Grant Award 1987