A Re-Evaluation of Dopamine-Acetylcholine Interaction in the Basal Ganglia

Grant Type
Grant Year
Institution Location
Institution Organization Name
University Center for Pharmacy The Netherlands
Investigators Name
DeBoer, Peter, PhD

Small molecules (neurotransmitters) like dopamine and acetylcholine play a role in the transduction of signals from one neuron to another by acting at binding sites (receptors). Ample evidence exists to implicate dopamine in the neurochemical pathology of Tourette’s disorder, whereas the role of acetylcholine is much less clear. Nevertheless, an antagonistic interaction between these two neurotransmitter systems is well documented, especially in a brain structure known as the striatum. A method called brain microdialysis has been developed during the past ten years which allows the study of neurochemical events in freely moving animals.. Using this technique it was found that the interaction between dopamine and acetylcholine was not simply an antagonistic one: dopamine exerts its effect on striatal acetylcholine by binding to two sites, DI and D2 respectively. Dopamine D2 receptor activation decreased the output of acetylcholine, whereas dopamine DI receptor activation increases the output of acetylcholine from the striatum. Besides the opposite effects of dopamine DI and D2 receptors on striatal acetylcholine, the receptor sites seem to be localized in different parts of the brain. One of the aims of the present project is now to determine the neuroanatomical basis of the Di/D2 mediated modulation of striatal acetylcholine. Nerve cells generally release neurotransmitters at their terminal region. A curious thing about dopaminergic neurons is their ability to release dopamine both at their terminal region and at their cell bodies lying in the substantia nigra (black substance). This phenomenon leads to the second goal of this study: to determine the mechanisms regulating the release of dopamine at both sites and the relative contribution of dopamine released at each site to the regulation of striatal acetylcholine. These studies will contribute to a better understanding of the neurobiology of dopamine-acetylcholine interactions and may help to explain the sometime conflicting results obtained with drugs interfering with acetylcholine in Tourette’s disorder. Peter DeBoer, M.Sc. University Center for Pharmacy, Groningen, The Netherlands Award $19,650 – Fellowship (2nd yr.) Tourette Association of America Inc. – Research Grant Award 1991