Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Grabbing addiction by the tail

28.11.2005


Canadian scientists have developed some clever molecular trickery that is helping to reduce the drug cravings of addicted rats. One of the problems in addiction is that neurons in some parts of the brain lose glutamate receptors from the cell surface, and those receptors are important for communication between neurons. The researchers have sidestepped this problem by crafting a peptide that mimics a portion of the tail of the glutamate receptor and, once inside a neuron, serves as a decoy to prevent the loss of glutamate receptors.



Yu Tian Wang, an HHMI international research scholar, and colleagues at the University of British Columbia in Vancouver report their findings in the November 25, 2005, issue of the journal Science.

In addicted rats, cell-to-cell communication is compromised as a result of certain long-term changes at the level of individual neurons. Their research has produced a targeted drug that tricks brain cells into preventing those changes. "We think this is a good candidate for a drug against addiction that has very few side effects," said Wang, a neuroscientist . Although the initial studies are promising, Wang cautioned that the drug is in the early stages of development and is years away from testing in humans.


During addiction to drugs, cells in the nucleus accumbens – a tiny ball of tissue deep in the brain involved in pleasure and motivation – mis-communicate. Normally, one neuron triggers activity in a neighbor by using neurotransmitters such as glutamate. "This is the ’go’ signal," said Wang. "The receiving cell uses glutamate receptors on its surface to listen to the signal.

But after repeated abuse of a drug, cells in the nucleus accumbens internalize glutamate receptors, compromising their ability to listen to the signals. Earlier research showed that receptor internalization in addicted rats accompanies behavioral sensitization, a model of craving.

Until now, though, no one knew how these receptors were removed from the cell surface, whether the process could be halted, and, if it could, whether the addicted rats would exhibit fewer signs of behavioral sensitization. Wang’s research has made significant progress toward answering these questions.

The researchers began by building a peptide – a long molecule made from a string of amino acids – with a structure similar to the tail of the glutamate receptor that is anchored inside the cell. In addiction, cellular machinery tugs on this tail, pulling the entire receptor into the cell. Without its business end sticking out into the synapse, or space between neurons, the receptor no longer works.

Wang’s peptide tricks the cellular machinery into tugging on it instead of the receptor’s tail. "Once it gets inside the neuron, the peptide competes with the receptor for binding to the machinery," Wang explained. With the cellular machinery otherwise occupied, the glutamate receptors stay on the cell surface, where they continue to receive signals.

After confirming these results in cell cultures, Wang and colleagues tested the peptide in rats that had been given amphetamine once every other day for 20 days. During this period, the animals displayed stereotypical behavior such as repeated sniffing, licking, and grooming, indicating a craving for the drug. Such behavior parallels the compulsive thought patterns that people addicted to drugs experience, said Anthony Phillips, Wang’s colleague at the University of British Columbia and a co-author of the article.

After keeping the rats drug-free for 21 days, the researchers gave the animals a small amount of drug again. The rats immediately displayed intense stereotypical behavior – a sign of behavioral sensitization. The behavior meant that the glutamate receptors in the animals’ neurons were rapidly internalized, said Wang. "It’s the trigger that leads to sustained motivation to seek a drug."

In contrast, addicted animals who received an intravenous injection of the artificial peptide displayed no sensitized behavior. "The effect was immediate and very noticeable," said Wang.

There are several types of glutamate receptors involved in memory and learning, but because the artificial peptide specifically targets only the deleterious internalization process of addiction-affected neurons, and not normal receptor function, the animals who received it behaved normally and were able to learn as usual. "So far, we have not seen any obvious side effects at all," said Wang.

By inserting a tiny tube into the rats’ brains, the researchers delivered the peptide directly to the nucleus accumbens and to another area of the brain involved in reward and motivation, the ventral tegmental area. The peptide reduced the rats’ drug-seeking behavior only when injected into the nucleus accumbens, evidence that the structure is critical for the expression of some of the devastating behaviors of addiction.

Jennifer Donovan | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>