Protein Strengthens Link Between Addiction And Long-Term Memory

March 27, 1997

Johns Hopkins scientists have discovered a new protein, called Homer, that becomes active in rat brain cells during exposure to cocaine and during a lab model of long-term memory creation.

"Homer is one of the first links between drug addiction and long-term memory that directly acts on nerve cells' message-receiving structures," says Paul Worley, M.D., an associate professor of neuroscience and neurology. "As such, it could be an important step toward understanding the connections between addiction and memory, and toward developing new treatments for addiction."

In a study funded by the National Institute on Drug Abuse and published in Nature, he found Homer by exposing rat brain cells to cocaine and to a lab model of memory used by neuroscientists.

"We call the protein Homer because it homes in' on critical areas where messages are being passed between nerve cells," says Worley.

In the memory model, researchers stimulate a nerve cell with an electric current and measure the resulting transmission of information between neurons.

If the current is given often and rapidly enough over a period of time, the nerve cell activates a number of genes and makes a number of complex changes that allow it to communicate more quickly and more effectively.

Neuroscientists think the brain may use this and other similar processes to enhance or weaken connections between nerve cells, and that this may be a key to the creation of memory.

Worley's group found that nerve cells increased their Homer production levels nearly 50 times within minutes of their activation, and that Homer binds to a message receptor on the surface of excitatory nerve cells, the metabotropic glutamate receptor.

"We think with further research we may find that Homer allows these receptors to stay open longer or to open up more easily," says Worley. "We believe it does something to enhance message reception, and will provide fundamental insights into how the brain maintains long-term memories or becomes addicted to drugs like cocaine."

As scientists learn more about Homer's effects, and its links to other changes in the nerve cell, new targets for drug treatments may become available.

Under an agreement between Lynx Therapeutics, a California Company, and the Johns Hopkins University, Lynx has right of first refusal for licensing Homer. Worley serves as a consultant to Lynx, owns stock in Lynx, and has received Lynx stock options, which are subject to certain restrictions under University policy. This arrangement is being managed by the University in accordance with its conflict of interest policies.

Other authors on the Nature paper were Paul Brakeman, Anthony Lanahan, Richard O'Brien, Katherine Roche, Carol Barnes and Richard Huganir.


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