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 Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

nachricht NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological 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: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>