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Grabbing addiction by the tail

s 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 receive
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Source:Howard Hughes Medical Institute


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