 |
|
 |
|
|
 |
 |
 |
 |
 |
 |
 |
 |
|
 |
 |
 |
|
 |
 |
|
 |
 |
 |
 |
 |
SFN 2004 Abstracts
University of Colorado Health Sciences Center
TRANSPLANTATION OF STEM CELLS EXPRESSING THE HUMAN DOPAMINE TRANSPORTER INTO THE NUCLEUS ACCUMBENS TRANSIENTLY MODIFIES ALCOHOL PREFERENCES
Jones, T. Grammatopoulos, M. Yoshimura, B. Hoover, E. Snyder, N. Zahniser, B. Tabakoff, M. Zawada
University of Colorado Health Sciences Center, Denver, CO 80262
To determine whether dopamine (DA) levels in the mesolimbic system modulate the preference for alcohol, we have stably transfected C17.2 neural stems cells with the human dopamine transporter (hDAT) gene to generate the C17.hDAT stem cell line. We hypothesized that reduction of the extracellular DA levels via hDAT will alter alcohol preference. Several clones exhibited constitutive [3H]-DA uptake. A clone showing good survival after transplantation into one day old C57BL/6 mouse pups, functional dopamine uptake, and robust b-galactosidase expression was transplanted bilaterally into nucleus accumbens of adult C57BL/6 mice, one of the nuclei thought to affect ethanol preference. Prior to transplantation, mice were tested for ethanol preference using a two bottle choice paradigm. After 15 days of exposure, 90% of mice consumed more ethanol than water, with an average preference ratio of 0.77. Mice were split into three groups and transplanted with C17.hDAT cells, a mock-transfected C17.2 clone, or saline (sham transplant). After 3-day recovery, mice were again tested for ethanol preference for an additional 7 days. Mice receiving the C17.hDAT clone exhibited lower ethanol preference at the first time point tested (6 days after surgery), but their preference gradually increased to match that of the sham or mock transfected controls by the termination of the study. Surviving C17.hDAT cells were identified in the transplants by X-gal staining. Transplantation of hDAT-expressing stem cells into brain nuclei known for their role in substance seeking should be a useful tool for exploring the role of DA in alcohol dependence. Supported by NIH AA13473.
INIA Home INIA Structure Administrative Core
Genetic Animal Models Core Gene Expression Core Imaging Core Neuroinformatics Core
Subgroups Current Grants Conference Abstracts Publications Links