Drug-proof zebrafish reveal secrets of addiction

Jul 31, 2009

The effects of amphetamines on gene expression in zebrafish have been uncovered. This new study, published in BioMed Central's open access journal Genome Biology, provides clues to the genetics that underlie susceptibility to addiction by describing the nad zebrafish mutant, which does not feel the rewarding effects of the drugs.

Katharine Webb, from the German Research Center for Environmental Health, Helmholtz Zentrum München, worked with an international team of researchers to carry out the experiments. She said, "Addictive drugs all trigger a sequence of widespread long-lasting consequences on brain physiology, most of which are only partially understood. Because a major step in the development of addiction is the switch from drug use to drug abuse, we aimed to gain insight into the mechanisms triggering the initiation of addictive behaviour".

The team used the mutagenic chemical ENU to generate hundreds of mutant zebrafish. From these, they bred a line that did not respond to amphetamine administration (despite the presence of the drug in the fish's brain) but that appeared to be normal in all other ways. As amphetamine is experienced as pleasurable, amphetamine response was determined by measuring whether fish chose to move to a half of the tank where the drug had been given out.

By comparing these drug-proof nad mutants to fish with a normal response, Webb and her colleagues discovered a set of 139 genes that respond inappropriately to amphetamine in nad mutants, without being altered under normal conditions in either genotype. In addition to genes involved in pathways classically associated with reward, this gene set shows a striking enrichment in transcription factors that are specifically known for their involvement in . Even more interestingly, as the authors demonstrate, several of these genes are expressed in neurogenic domains of the adult - these are domains where neurons are generated from during adulthood. According to the researchers, " These factors, which are also dramatically down-regulated by amphetamine, can serve as valuable new entry points into studying the link between adult neurogenesis and addiction".

These results identify a new network of coordinated gene regulation that influences the response to amphetamine and may underlie the susceptibility to addiction.

More information: reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine, Katharine J Webb, William HJ Norton, Dietrich Trümbach, Annemarie H Meijer, Jovica Ninkovic, Stefanie Topp, Daniel Heck, Carsten Marr, Wolfgang Wurst, Fabian J Theis, Herman P Spaink and Laure Bally-Cuif, (in press), http://genomebiology.com/

Source: BioMed Central (news : web)

Explore further: 'Hairclip' protein mechanism explained

add to favorites email to friend print save as pdf

Related Stories

Cocaine-linked genes enhance behavioral effects of addiction

May 13, 2009

New research sheds light on how cocaine regulates gene expression in a crucial reward region of the brain to elicit long-lasting changes in behavior. The study, published by Cell Press in the May 14th issue of the journal ...

Meth addiction mechanism discovered

Apr 09, 2008

Researchers have identified, for the first time, long-term changes in the brain circuitry of methamphetamine-addicted mice that can explain why the craving of addiction is so stubborn and long-lived. The research could lead ...

Research Links Change in Brain with Addiction

Feb 01, 2007

A researcher at the University at Buffalo's Research Institute on Addictions (RIA) has found a change in the brain that occurs after drug use and that may contribute to drug addiction.

Assembling the jigsaw puzzle of drug addiction

Jan 05, 2008

Using an integrative meta-analysis approach, researchers from the Center for Bioinformatics at Peking University in Beijing have assembled the most comprehensive gene atlas underlying drug addiction and identified five molecular ...

Recommended for you

'Hairclip' protein mechanism explained

12 hours ago

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

Discovery in the fight against antibiotic-resistant bacteria

14 hours ago

For four years, researchers at Universite catholique de Louvain have been trying to find out how bacteria can withstand antibiotics, so as to be able to attack them more effectively. These researchers now understand how one ...

Stem cells born out of indecision

14 hours ago

Scientists at the University of Copenhagen have gained new insight into embryonic stem cells and how blocking their ability to make choices explains why they stay as stem cells in culture. The results have just been published ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.