Brain's Reward Circuitry Revealed in Procrastinating Primates - Article Psychiatric Disorders
Article: Brain's Reward Circuitry Revealed in Procrastinating Primates
Using a new molecular genetic technique, scientists have turned procrastinating primates into workaholics by temporarily suppressing a gene in a brain circuit involved in reward learning. Without the gene, the monkeys lost their sense of balance between reward and the work required to get it, say researchers at the NIH's National Institute of Mental Health (NIMH).
"The gene makes a receptor for a key brain messenger chemical, dopamine," explained Barry Richmond, M.D., NIMH Laboratory of Neuropsychology. "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. 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."
Richmond, Zheng Liu, Ph.D., Edward Ginns, M.D., and colleagues, report on their findings in the August 17, 2004 Proceedings of the National Academy of Sciences, published online the week of August 9th.
Richmond's team trained monkeys to release a lever when a spot on a computer screen turned from red to green. The animals knew they had performed the task correctly when the spot turned blue. A visual cue a gray bar on the screen got brighter as they progressed through a succession of trials required to get a juice treat. Though never punished, the monkeys couldn't graduate to the next level until they had successfully completed the current trial.
As in a previous study (
Molecular geneticist Ginns, who recently moved from NIMH to the University of Massachusetts, adapted an approach originally used in mice. He fashioned an agent (DNA antisense <
"The monkeys became extreme workaholics, as evidenced by a sustained low rate of errors in performing the experimental task, irrespective of how distant the reward might be," said Richmond. "This was conspicuously out-of-character for these animals. Like people, they tend to procrastinate when they know they will have to do more work before getting a reward."
To make sure that it was, indeed, the lack of D2 receptors that was causing the observed effect, the researchers played a similar recombinant decoy trick targeted at the gene that codes for receptors for another neurotransmitter abundant in the rhinal cortex: NMDA (N-methlD-aspartate). Three monkeys lacking the NMDA receptor in the rhinal cortex showed no impairment in reward learning, confirming that the D2 receptor is critical for learning that cues are related to reward prediction. The researchers also confirmed that the DNA treatments actually affected the targeted receptors by measuring receptor binding following the intervention in two other monkeys' brains.
"This new technique permits researchers to, in effect, measure the effects of a long-term, yet reversible, lesion of a single molecular mechanism," said Richmond. "This could lead to important discoveries that impact public health. 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," suggested Richmond.
"For example, people who are depressed often feel nothing is worth the work. People with OCD 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."
Also participating in the research were: Drs. Elisabeth Murray, Richard Saunders, Sara Steenrod, Barbara Stubblefield, Deidra Montague, NIMH.
NIMH is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.
Source: National Institutes of Health
Cache Date: December 16, 2004
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