Ulrike A. Heberlein
Howard Hughes Medical Institute
|
Primary Section: 26, Genetics Secondary Section: 24, Cellular and Molecular Neuroscience Membership Type:
International Member
(elected 2010)
|
Research Interests
The overall goal of our research is to understand the neural and molecular mechanisms that contribute to drug addiction, with the ultimate goal of providing targets for therapeutic intervention and diagnosis of risk factors. In the mid-nineties our laboratory introduced a new model organism to the field of drug addiction, the fruit fly Drosophila melanogaster, which provides unparalleled accessibility to genetic, behavioral and molecular analyses. At that time, we made two major assumptions: First, we assumed that the mechanisms by which drugs act in the nervous system to regulate behavior would be evolutionarily conserved. Thus, unbiased genetic screens -- made feasible by the ease, speed, and low cost of Drosophila research -- would provide novel insights into the molecular mechanisms underlying drug-related behaviors in mammals. Second, we assumed that understanding relatively simple drug-induced behaviors, such as intoxication and tolerance, would provide insights into the more complex processes regulating drug reward and addiction in mammals. Indeed, the Drosophila studies have shown that behaviors induced by acute or intermittent drug exposure are surprisingly similar in flies and mammals, and that many of the genes, neurotransmitters and second messenger systems that mediate these behaviors are conserved. Thus, while the addiction-related studies in Drosophila are still relatively new, they strongly suggest that this simple model system will provide novel information that can be (and has been) transferred to mammals. More recently, we have developed more complex assays that allow us to measure "addiction like' behaviors in flies. These include assays for ethanol consumption and preference (feeding and drinking), relapse, and reward (conditioned odor preference). We are also beginning to study how prior experiences, such as social defeat and stress, affect ethanol preference and reward. Finally, we have developed Drosophila models for ethanol-induced neurotoxicity and fetal alcohol syndrome, and have found that some of the underlying mechanisms are conserved with mammals. As is the case in most areas of biology, having a good assay is the first and most crucial step needed before delving into the underlying mechanisms.
