Cocaine addiction wreaks profound changes on the brain, hijacking reward circuits and depressing inhibitory loops to the point that drug seeking and taking become central drivers of behavior. While mammalian models are useful for mapping out the neural complexity of these behaviors, insights into the molecular basis of drug abuse can often be garnered from simple models, such as the fruitfly, Drosophila. In the open-access journal PLoS Biology, Ulrike Heberlein and colleagues describe their discovery of a new gene that modulates sensitivity to cocaine within the cells of the fruitfly's internal clock. They further show that the cells' role in regulating cocaine sensitivity is distinct from its function as a timekeeper.

One known effect of cocaine on Drosophila is loss of "negative geotaxis," or wall climbing, in response to startle. Using this behavior to screen 400 different mutants, the researchers identified seven with an increased response to cocaine, and for two of these, the disrupted gene was the same, Lmo.

While Lmo is found throughout the body, it is enriched in the brain, and its cocaine-related effects appear to localize in the ventral lateral neurons (LNvs), which provide the fly with an internal clock, driving circadian activities even in the absence of light. However, it appears that these neurons modulate cocaine sensitivity independently of their role in controlling circadian rhythms.

Because Lmo-related proteins are found in key areas of mammalian brains, these results may have important implications for understanding innate differences in sensitivity to cocaine in humans, and potentially provide targets for development of drugs to treat or prevent addiction.

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Contact: Paul Ocampo
pocampo@plos.org
1-415-624-1224
Public Library of Science
22-Nov-2004

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