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 Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>