Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Flies on crack

23.11.2004


New study isolates gene mutation responsive to cocaine



Researchers at the University of California, San Francisco (UCSF) and New York University have discovered a gene mutation in fruit flies that alters sensitivity to crack cocaine and also regulates their internal body clock. The findings, reported in the December issue of Public Library of Science (PLoS) Biology, may have implications for understanding innate differences in sensitivity to cocaine in humans, potentially providing targets for development of drugs to treat or prevent addiction.

Headed by UCSF’s Ulrike Heberlein, the research team discovered a mutation of the Drosophila LIM-only (Lmo) gene. Normal fruit flies increase their activity when exposed to low doses of crack cocaine over a one-minute period. At medium levels, fruit flies exhibit frenzied, jerky motions. At high doses, the flies become immobile. However, flies with the Lmo gene mutated were much more sensitive to crack cocaine and became immobile at much lower levels than normal fruit flies.


Heberlein’s group also showed that Lmo is normally produced in the pacemaker neurons that control 24-hour--or circadian--rhythms of sleep/wake cycles in flies. Comprising about 10 cells per hemisphere, these neurons provide the fly with an internal clock, driving circadian rhythms of behavior even in the absence of light. While Lmo is found throughout the body, it is enriched in the brain. By expressing normal Lmo in over-sensitive mutants, the researchers discovered that Lmo’s cocaine-related effects were localized to the circadian pacemaker neurons.

The researchers then asked if the Lmo mutations also affect the normal rhythms in circadian behavior. Subsequently, NYU’s Justin Blau, an assistant professor of biology, found that many Lmo mutant flies no longer had clear rhythms of sleep/wake cycles. Together, the two sets of findings showed that the new gene modulates sensitivity to cocaine within the cells of the fruit fly’s internal clock.

Previous researchers had only been able to demonstrate that cocaine enhances the mammalian brain’s ability to block re-uptake of dopamine by cells in a brain region called the nucleus acumbens. But numerous experiments show this is not the whole story. The latest study by Heberlein, Blau, and their colleagues reveal a more complex neurological process.

From 400 different mutants, they identified seven with an increased response to cocaine, and for two of these, the disrupted gene was the same--Lmo. The Lmo protein, whose levels were reduced by the mutations, is known to regulate certain transcription factors during development. However, no developmental defects were detected in the loss-of-function mutants that might explain the cocaine effect. They also found that a third mutation in the same gene, previously associated with disruption in wing formation in fruit flies, increased levels of the Lmo protein and decreased response to cocaine. Thus, they concluded that Lmo appears to play a central role in regulating cocaine sensitivity.

The researchers suggested that because Lmo-related proteins are found in mammalian brains, the results may have implications for understanding innate differences in sensitivity to cocaine in humans, potentially providing targets for development of drugs to treat or prevent addiction.

"It’s been established the some individuals may be predisposed to addiction," Blau added. "These findings suggest that a specific genetic make-up in humans could further explain why some individuals are more susceptible than others."

James Devitt | EurekAlert!
Further information:
http://www.nyu.edu

More articles from Life Sciences:

nachricht Clock stars: Astrocytes keep time for brain, behavior
27.03.2017 | Washington University in St. Louis

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Electrical 'switch' in brain's capillary network monitors activity and controls blood flow

27.03.2017 | Health and Medicine

Clock stars: Astrocytes keep time for brain, behavior

27.03.2017 | Life Sciences

Sun's impact on climate change quantified for first time

27.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>