Neuroleptic drugs like haloperidol are widely used in the treatment of Tourette’s disorder. Because the effect of this class of drugs is blockage of dopaminergic neurotransmission in the brain, a role for dopamine in the neurochemical pathology of Tourette’s disorder has been proposed. One of the brain areas that receives a rich dopaminergic projection is the striatum. An antagonistic interaction of dopamine with another striatal neurotransmitter, acetylcholine, is now well documented. However, with the advent of new methods to study dopaminergic and cholinergic systems, it has been shown that the interaction between dopamine and acetylcholine is more complex than previously assumed. Two pharmacologically distinct dopamine receptors, the D-1 and the D-2 receptor, exert antagonistic effects on the output of acetylcholine in the striatum. We propose that these antagonistic effects originate in different brain areas, and one of the goals of this project is to study the brain substrates involved in the dopaminergic regulation of striatal acetylcholine release. Furthermore, we plan to characterize the interaction between dopamine and acetylcholine in more detail. These studies will contribute to a better understanding of the neurobiology of the dopaminergic cell groups in the brain and their interactions with other brain systems, especially cholinergic systems. Since these cell groups may be involved in neurochemical pathology of Tourette’s disorder, knowledge of these systems is of importance for a better understanding of the disorder and in order to find new targets for drug-development. Peter DeBoer, Ph.D. Rutgers University, Newark, NJ Award $21,120 Tourette Association of America Inc. – Research Grant Award 1992