Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Using fruitflies to examine alcohol tolerance

15.10.2004


Rapid and chronic tolerance appear to operate via different neurobiological mechanisms and genes

  • Alcohol tolerance both promotes and facilitates the increasing consumption of alcohol.
  • New research uses fruitflies to examine the mechanistic and genetic underpinnings of different forms of tolerance.
  • Findings suggest that rapid and chronic tolerance are partially distinct in mechanistic terms, as well as genetically distinguishable, from one another.

"Alcohol tolerance" refers to the diminishing physiological, behavioral and subjective effects of alcohol that occur with repeated exposure to the drug. A study in the October issue of Alcoholism: Clinical & Experimental Research uses flies to define the genetic and mechanistic underpinnings of different forms of tolerance. "Tolerance is important and relevant to human drinking because its development both promotes and facilitates increasing intake of alcohol," said Karen H. Berger, senior scientist at the Ernest Gallo Clinic and Research Center. "Rapid and chronic tolerance are produced by different types of previous experience with alcohol. ’Rapid tolerance’ results from a single intoxicating dose, whereas ’chronic tolerance’ is produced by repeated or continuous exposure to alcohol over longer periods of time."

"Theories about the root causes of alcoholism often invoke the development of tolerance as an important event," added John Crabbe, director of the Portland Alcohol Center. "For example, if one must keep drinking more in order to get the same happy feeling, it is easy to see how with greater tolerance there could be a greater chance of developing into a problem drinker. Also, anyone who has developed enough of a drinking problem to earn a diagnosis of alcohol dependence or alcoholism has developed a great deal of chronic tolerance. Thus, tolerance is not only a part of the diagnostic criteria for alcohol dependence and alcoholism, but it may also be important for understanding the changes in brain mechanisms that lead some to develop problems with alcohol."


"The fruitfly Drosophila melanogaster is one of the most intensively studied organisms in biology, and has provided essential insights into developmental and cellular processes that are shared with higher animals, including humans," said Berger. "Flies have a relatively sophisticated nervous system and are capable of many well-characterized complex behaviors, including response to drugs of abuse such as alcohol, cocaine, PCP, and nicotine. The popularity of flies as a model system is in large part due to the availability of powerful genetic tools that enable the identification and analysis of genes. Additionally, flies can be grown for experiments relatively rapidly and inexpensively."

For this study, researchers exposed flies to either a single intoxicating dose of alcohol (rapid tolerance), or to a low concentration of alcohol continuously during a 48-hour period (chronic tolerance). Tolerance was measured based on increased speed of recovery from subsequent intoxication relative to alcohol-naïve controls, and also by a second assay measuring delayed onset of intoxication. "In flies, like mammals, we have found that different types of alcohol exposure can produce tolerance," said Berger. "Most strikingly, our results suggest that there are differences in the mechanisms underlying tolerance produced by different protocols of previous alcohol exposure. First, pre-treatment with a drug inhibiting protein synthesis blocked the development of chronic but not of rapid tolerance. Second, a fly mutant that lacks octopamine – a neuromodulator that serves as the fly version of norepinephrine – showed reduced rapid tolerance but unchanged chronic tolerance. In sum, two different lines of experiments provide pharmacological and genetic support for the idea that rapid and chronic tolerance may utilize at least partially distinct pathways in flies."

"The most provocative result in this study is the suggestion that rapid and chronic tolerance are mechanistically distinct," said Crabbe. "This is interesting because the rodent literature suggests that … rapid and chronic tolerance appear likely to represent early and later versions of the same set of brain adaptations to alcohol. The second finding of interest concerns mutant flies with a defective ability to produce octopamine. By testing flies with mutations for many other genes, the authors will be able to test more rigorously their suggestion that different genetic pathways underlie these two forms of tolerance."

Crabbe had specific suggestions for future research in this area. "The authors of this study distinguish between two types of alcohol tolerance, rapid and chronic," he said. "There is a third general type of tolerance which occurs during a single exposure to alcohol, acute functional tolerance, which was not studied here." All three types have been demonstrated in humans, he added. "If researchers could develop an assay for acute functional tolerance in flies, they would then have a complete set of behavioral assays in parallel to those who work with rodents," said Crabbe. "Then, given the spectacular power of fly genetics, they could analyze the genetic contributions to these three types of tolerance with a thoroughness and speed that greatly outstrips the abilities of those scientists using rodents. By identifying specific genes and pathways, they could settle for once and for all whether these are simply way stations on a single continuum of neural adaptation, or three different sets of brain adaptations of alcohol. In the end, the goal is to move beyond our current understanding, that is, that some humans possess a genetically influenced tendency to develop alcoholism and others do not. The great similarity among the genomes of flies, mice and humans may very well help us to do so."

Karen H. Berger, Ph.D. | EurekAlert!
Further information:
http://www.egcrc.org
http://www.ohsu.edu

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>