A peptide might prevent the development of addiction.

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.

One obvious problem with this approach is that peptides are hard to deliver. Diabetics have to take insulin shots because the insulin peptide would get digested and broken up if taken orally. So a peptide treatment would probably have to be taken by syringe. Still, diabetics manage to do this and some addicts have plenty of experience with syringes.

Another potential problem is that the peptide might interfere with normal learning or other normal on-going neuronal processes. But such an interference might be worth it given the damage that amphetamine use causes to people's brains and their lives and the lives of other people around them.

The biggest question I see here is whether the peptide will work on existing addicts. Most people aren't going to go to the doctor and say "Hey, I'm about to spend several months abusing amphetamine. Could you prescribe me that peptide drug that'll prevent addiction from developing?". I suspect the peptide will do less to reverse addiction than it will to prevent it. However, the press release isn't clear enough on the protocol used to tell if that is the case.

The peptide has a piece that looks like the glutamate receptor and so competes with the glutamate receptor for getting pulled into the cell.

Wang's team developed a peptide that serves as a decoy to prevent the cell from pulling glutamate receptors in from their surfaces.

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.

The peptide prevented sensitization of the rats to amphetamine and therefore probably would block the development of cravings.

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.

An ideal anti-addiction drug would allow someone in the early stages of addiction to pull out when they realize they've become hooked. But if such a drug existed how many early stage addicts could be convinced to use it before they racked up a lot of brain damage?