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 On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

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: 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...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

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

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

How gut bacteria can make us ill

18.01.2017 | Life Sciences

On track to heal leukaemia

18.01.2017 | Health and Medicine

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>