Recent diffusion tensor imaging (DTI) studies fnsm our laboratory and others have demonstrated significantly reduced fractional anisotropy (FA) in the corpus callosum in cocaine-dependent subjects relative to controls. The changes in FA have been interpreted as an indication of altered myelin. The specific underlying neuropathology of these white matter changes and if these pathological changes can be altered by cocaine abstinence or novel phramacotherapy, however, remain to be determined. Understanding the pathological changes between nornial, healthy individuals and cocaine-addicts is not simple because of difficulties in creating a completely controlled environment. In addition, histologic confirmation of the proposed pathologic mechanism is difficult to realize in humans. In the proposed translational studies, using multi-modal magnetic resonance imaging and end point histology in rodents treated with chronic cocaine, we will determine the effects of 1) dose of cocaine and method of administration on a) regional brain atrophy measured on high resolution structural MRI with tensor based morphometry, b) white matter pathology as measured by DTI and magnetization transfer ratio, c) regional cerebral blood flow as determined by MRI-based arterial spin labeling, and d) metabolite concentrations as determined by proton magnetic resonance spectn^scopy and 2) administration of the novel adenosine A2A receptor antagonist SYN115 on cocaine associated white matter pathology, regional brain volumes and regional cerebral blood flow. These multi-modal studies in rodents should help characterize neuropathological changes and institute rational-based treatments in human cocaine abusers.

Public Health Relevance

Cocaine dependence is associated with changes in brain structure and function. This study will use animal models of cocaine use to determine the underiying pathology of these changes and determine if novel medications could reverse these pathological changes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA009262-18
Application #
8378468
Study Section
Special Emphasis Panel (ZDA1-EXL-T)
Project Start
Project End
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
18
Fiscal Year
2012
Total Cost
$312,974
Indirect Cost
$123,840
Name
University of Texas Health Science Center Houston
Department
Type
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
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