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.
Citation: Tsai L, Bainton R, Blau J, Heberlein U (2004) Lmo Mutants Reveal a Novel Role for Circadian Pacemaker Neurons in Cocaine-Induced Behaviors. PLoS Biol 2 (12): e408.
Contact:
Ulrike Heberlein
University of California, San Francisco
1550 4th Street, Room 445
San Francisco, CA 94143-2822
1-415-502-1717
ulrike@itsa.ucsf.edu
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