Funding Agency:

National Institutes of Health, National Institute of Neurological Disorders and Stroke (Grant No. R01 NS040125)

Total Project Period:

03/01/00 - 03/31/09

Total Project Award:

$3,020,900

Principal Investigator:

C. Edward Dixon, PhD

Co-Investigators:

Hong Q. Yan, MD, Patrick M. Kochanek, MD (Department of Critical Care Medicine), Edwin Jackson, PhD (Department of Pharmacology), Larry Jenkins, PhD

Project Summary:

Numerous studies have demonstrated an antagonistic interaction between specific adenosine A2A receptor (A2AR) and dopamine (D2R) subtypes. Because of this relationship, it is possible to increase the affinity of D2 receptors and likely activate D2R coupled intracellular cascades via blockade of A2ARs. Therefore, the use of A2AR antagonists, which are a treatment target for Parkinson’s disease (PD), a disease associated with DA hypofunction, may be a novel therapeutic target for enhancing DA agonist therapy after TBI. We propose to extend our previous findings in the dopaminergic system to hypothesize that persistent functional deficits following TBI may be, at least partially, attenuated by adenosine A2AR modulation of D2R function. The results of these studies will expand our knowledge of striatal function after TBI and provide initial preclinical evidence to support clinical investigation into adenosine enhanced DA agonist therapies for chronic TBI.