Source: CNN
Date: 11 August 2004

Gene blocking turns monkeys into workaholics


WASHINGTON (Reuters) -- Procrastinating monkeys were turned into workaholics using a gene treatment to block a key brain compound, U.S. researchers reported on Wednesday.

Blocking cells from receiving dopamine made the monkeys work harder at a task -- and they were better at it, too, the U.S. government researchers found.

Dr. Barry Richmond and colleagues at the National Institute of Mental Health used a new genetic technique to block the D2 gene.

"The gene makes a receptor for a key brain messenger chemical, dopamine," Richmond said in a statement. Dopamine is a message carrying chemical associated with rewards, movement and a variety of other important functions.

"The gene knockdown triggered a remarkable transformation in the simian work ethic. Like many of us, monkeys normally slack off initially in working toward a distant goal," he added.

For their study, Richmond and colleague used seven rhesus monkeys. They had to push a lever in response to visual cues on a projection screen, and got a drop of water as a reward.

"They work more efficiently -- make fewer errors -- as they get closer to being rewarded. But without the dopamine receptor, they consistently stayed on-task and made few errors, because they could no longer learn to use visual cues to predict how their work was going to get them a reward."

Writing in the Proceedings of the National Academy of Sciences, Richmond and colleagues said they were trying to figure out how D2 is involved in a type of learning.

Humans and monkeys both use this learning, which involves looking at how much work there is, visually, and deciding how long it will take to complete it.

Monkeys and humans both tend to wait until the last possible minute to finish up the work, and become very adept at estimating how long they have.

Molecular geneticist Edward Ginns created a DNA antisense agent that tricked brain cells into turning off their D2 receptors -- which are molecular doorways used by dopamine to get into cells.

Antisense involves making a kind of mirror image molecule that looks like a strand of DNA and works to block a gene's action.

Although some employers might take a distinct interest in the work, the NIMH team said they are hoping to understand mental illness.

"In this case, it's worth noting that the ability to associate work with reward is disturbed in mental disorders, including schizophrenia, mood disorders and obsessive-compulsive disorder, so our finding of the pivotal role played by this gene and circuit may be of clinical interest," Richmond said.

"For example, people who are depressed often feel nothing is worth the work. People with obsessive-compulsive disorder work incessantly; even when they get rewarded they feel they must repeat the task. In mania, people will work feverishly for rewards that aren't worth the trouble to most of us."

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