Grabbing addiction by the tail

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 recepto

Contact: Jennifer Donovan
Howard Hughes Medical Institute

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