Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify drug-tolerance mechanism in flies

30.11.2004


A protein found on the surface of nerve cells makes fruit flies tolerant to a drug after just a single, brief exposure, which may reveal ways to address this early step toward addiction in humans.



Neuroscientist Nigel Atkinson at The University of Texas at Austin and his laboratory determined this by studying the response of fruit flies (Drosophila) to a 15-minute exposure to benzyl alcohol coated on the inner walls of test tubes. Flies that had had one previous exposure to the organic solvent recovered more quickly from being knocked out by the drug than flies that were first-timers. The flies that developed tolerance also had increased activity of the slo gene. The gene produces the surface protein, which helps stimulate signaling between nerve cells in the brain.

Genetically modified flies that lacked the slo gene failed to develop tolerance, while flies modified to have increased slo activity were more drug resistant than normal, providing added proof of the gene’s importance for tolerance. Because the human slo gene is almost identical to the one in fruit flies, Atkinson said, "If we could describe the series of steps involved in changing slo gene expression, then all the components involved in producing that change could become potential targets for anti-addiction drugs."


The findings will be published online the week of Monday, Nov. 29, by the Proceedings of the National Academy of Sciences.

Benzyl alcohol (BA) is usually used as an anesthetic. Although few people seek it as a drug, the same behavioral and genetic effects were found when flies were exposed to the addictive chemical in glue or other addictive organic solvents. Initially, flies placed inside BA-laden test tubes began moving quickly and climbing the walls. Within minutes, this excited phase ended and they started falling off the walls and stumbling, before passing out. "They start tripping more and taking longer and longer to get up, basically acting like a drunk at a college party," Atkinson said.

The reverse behavior happened during recovery from the drug. The flies began stumbling around and then climbing the test-tube walls within minutes. The flies that had previously been exposed to BA recovered much more rapidly than their drug-free counterparts. The researchers have since found that this tolerance lasts for more than seven days. "These findings show that very short exposures to drugs have very long-term effects," he said.

Genetic analyses of BA-exposed flies revealed that the slo gene behaved differently during the excitement and sedative phases of drug intoxification. During excitement, the level of slo activity dropped by 75 percent, whereas its level was more than twice as high as normal when flies became sedated.

Atkinson and his co-authors suggest that the protein produced by slo serves as a thermostat to control how actively nerve cells transmit signals to other nerve cells. The slo protein serves as a portal, or channel, on the surface of nerve cells that permits potassium to enter the cells in a way that modifies electrical signaling. The researchers think that when a drug causes nerve cells to fire too rapidly, slo levels are decreased to produce fewer portals and dampen the drug’s effect. Having the slo gene instead become more active when the nervous system is sedated by a drug would help overcome that sedation, and underlies the development of tolerance.

"We think that producing more channels is a way to make the nervous system fire more excitedly, and decreasing the number of channels would make the nervous system less excited," Atkinson said, noting that the slo channel responses likely act to compensate for other genes that are directly excited or sedated by drugs. "It’s not going to be a simple story where there’s just one protein involved in a response to a drug," he said.

Because slo is central to tolerance development, Atkinson’s laboratory plans to identify the factors that regulate the slo gene in response to drug intoxification. Fruit flies are easy to genetically manipulate, so the work could rapidly identify which of those factors would be good targets for future drug research.

"We will use Drosophila to answer these regulatory questions," Atkinson said. "Once we understand what happens in flies we can more easily ask if the same thing happens in mammals."

Barbra Rodriguez | EurekAlert!
Further information:
http://www.utexas.edu

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

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

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>