Ulrike Heberlein,
University of California at San Francisco, USA
Drug addiction is a chronic and relapsing mental illness characterized by compulsive drug use despite serious negative consequences. The cost to society is enormous, yet few treatment strategies exist and those that are available have so far met with very limited success. There is strong evidence from family, twin, and adoption studies, that genetic as well as environmental factors contribute to the risk for drug addiction. It is also well established that multiple genetic loci contribute to this risk and that the constellation of loci involved differs among affected individuals, making identification of specific "addiction genes" a difficult endeavor.
These complexities, together with the high cost of human studies, have led to the development of animal models. Most prominently, rodent models have been used extensively to study how drugs of abuse exert their acute, chronic, and addictive effects. In the last decade, the invertebrate model organisms Drosophila melanogaster and C. elegans – highly accessible to genetic, molecular and behavioral analyses - have been advanced as powerful new animal models to study how abused drugs function in the nervous system to affect behavior. It is becoming increasingly clear that the behaviors induced by acute and chronic drug administration are remarkably similar in invertebrates and mammals, and that at least some of the underlying molecular and neurochemical mechanisms are also conserved.
The use of completely unbiased genetic screens - aided by the ease, quickness, and low expense of invertebrate studies – has led to the identification of novel genes regulating drug-related behaviors. The next phase is to validate these candidate genes, and the signaling pathways and biological processes in which they function, in mammalian model systems and humans. Drug addiction is still not broadly acknowledged as a disease and the associated stigma has hampered the advancement of scientific approaches to treatment. Research on the mechanisms by which abused drugs affect nervous system function and identification of the genetic risk factors should provide novel therapeutic targets and, hopefully, an effective treatment for drug addiction in the near future. |
