D2 Receptor Regulation of Arachidonic Acid Metabolism and Excitability in the Nucleus Accumbens

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Tennessee
Investigators Name
Surmeier, D. James, PhD

Although it appears that Tourette Syndrome (TS) does not involve a mutation of the D2 receptor gene (13), an understanding of the molecular events underlying the actions of D2-class antagonists should: 1) foster the development of more effective therapies for TS and 2) help identify those signaling elements that are defective in TS. Our central hypotheses are that 1) D2-class receptors in NAc neurons enhance the evoked release of arachidonic acid (AA) and its metabolites and 2) these metabolites reduce cellular excitability by modulating voltage-dependent calcium conductances and glutamate receptors. If our hypotheses are correct, then defects in AA metabolism or the linkage between D2-class receptor activation and AA metabolism become etiological candidates in TS. Establishing such a connection would open several therapeutic avenues for TS patients employing an already well-developed collection of agents for manipulating eicosanoid metabolism. Genetic studies of TS and associated gene therapies could also be helped immediately by linking D2-class receptors and eicosanoids. Base sequences for PLA2 isoforms and 5-, 12- and 15-lipoxygenases isoforms are available, making genetic mapping studies feasible. D. James Surmeier, Ph.D. University of Tennessee Health Science Center, Memphis, TN Award $10,000 Tourette Association of America Inc. – Research Grant Award 1992