The scientists delivered the gene by first inserting it into a virus that had been rendered harmless. They then injected the virus directly into the rats ™ nucleus accumbens, the brain ™s pleasure center. The idea behind this type of gene therapy is to use the virus as a vector to carry the gene to the brain cells, which can then use the genetic instructions to make the D2 receptor protein themselves.

As an additional measure in this study, the scientists used micro-positron emission tomography (microPET) imaging to non-invasively assess the effects of chronic alcohol consumption on D2 receptor levels in alcohol-preferring and non-preferring rats. They measured D2 levels seven weeks after the gene therapy treatment (well after the effects of gene therapy had worn off). D2 receptor levels in alcohol-preferring rats were significantly lower (about 16 percent) compared to that in non-preferring rats. These levels were similar to previous data in na ve preferring and non-preferring rats.

In future studies, the D2 connection to alcoholism will be examined in transgenic mice that are totally depleted of D2. In addition, the scientists plan to develop a second generation D2 vector approach that will provide a longer period of treatment.

These findings further support our hypothesis that high levels of D2 are causally associated with a reduction in alcohol drinking and may serve as a protective factor against alcoholism, Thanos said.

This study was funded by the Office of Biological and Environmental Research within the Department of Energy ™s Office of Science and by the National Institute of Alcohol Abuse and Alcoholism within the National Institutes of Health.