posted on Aug, 13 2004 @ 01:33 PM
Here's the origin(NIMH):
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
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
As in a previous study using the same task, the monkeys made progressively fewer errors with each trial as the reward approached, with the fewest
occurring during the rewarded trial. Previous studies had also traced the monkeys' ability to associate the visual cues with the reward to the rhinal
cortex, which is rich in dopamine. There was also reason to suspect that the dopamine D2 receptor in this area might be critical for reward learning.
To find out, the researchers needed a way to temporarily knock it out of action.
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 expression construct) that, when injected directly into the rhinal cortex of four trained monkeys, spawned a kind of decoy
molecule which tricked cells there into turning-off D2 expression for several weeks. This depleted the area of D2 receptors, impairing the monkeys'
reward learning. For a few months, the monkeys were unable to associate the visual cues with the workload—to learn how many trials needed to be
completed to get the reward.
"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.