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 Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>