Injections Temporarily Turn Slacker Monkeys Into Model Workers

Injections Temporarily Turn Slacker Monkeys Into Model Workers

LA Times Aug 12, 2004

Laboratory monkeys that started out as careless
procrastinators became super-efficient workers after
injections into their brains that suppressed a gene linked
to their ability to anticipate a reward.

The monkeys, which had been taught a computer game that
rewarded them with drops of water and juice, lost their
slacker ways and worked faster while making fewer errors.

Government researchers used a new technique to temporarily
block a gene, known as D2, that normally produces receptors
for the brain chemical dopamine--a component in the
perception of pleasure and satisfaction.

Terrence Sejnowski, a neurobiologist at the Salk Institute
for Biological Studies in La Jolla, called the experiment a
"tour de force" for opening a new way of modulating brain
chemistry. "The ability to block a specific type of receptor
in a specific part of the brain could allow a new generation
of therapeutics with fewer side effects," he said.

The results, reported Tuesday in the Proceedings of the
National Academy of Sciences, could also shed light on
mental illnesses that involve motivation, such as obsessive
compulsive disorder and mania.

It turns out that the work ethic of rhesus monkeys resembles
that of many humans.

"If the reward is not immediate, you procrastinate," said
Barry Richmond, a neurologist who led the study at the
National Institute of Mental Health.

The task at hand was a computer game in which a monkey,
perched in a plexiglass cage in front of a computer monitor,
would release a lever each time a red dot on the screen
turned green. Only quick responses counted.

The number of successes needed for a reward varied —
one, two or three. A gray bar on the monitor told the seven
monkeys in the experiment of their progress, brightening as
a drink became imminent.

Before their genetic treatment, the monkeys in the test
dawdled when the gray bar was dim. Only when it glowed did
they become conscientious.

All that changed after a snippet of DNA known as an
"anti-sense expression vector" was injected into a part of
the brain known as the rhinal cortex. The vector suppressed
the expression of the D2 gene for several weeks, hampering
the ability of the rhinal cortex to detect dopamine.

The monkeys no longer understood the meaning of the gray
bars. As a result, their interest never waned. They worked
their levers like obsessed gamblers, never knowing when the
jackpot would be delivered. They stopped only after their
thirst was quenched.

To the researchers, the results made sense.

Dopamine is related to the reward pathways in the brain. The
rhinal cortex is a part of the brain where meaning is
attached to recognized objects. The hardworking monkeys
acted as if their rhinal cortexes had been removed.

But don't expect any gene-suppressing injections for chatty
office workers or inattentive students.

"Perhaps they would look like manic people all the time,"
Richmond said.

The research could help in understanding the neural
circuitry in people who have any of a variety of disorders.

Schizophrenia and Parkinson's disease are related to
dopamine pathways.

Other illnesses are linked to some fault in the reward
circuitry of the brain. Manic people work even when the
rewards are insignificant. In depression, no amount of work
seems worth the reward. In obsessive compulsive disorder,
the rewards never seem to register. Drug abusers risk
danger for their reward.

The research also advances the use of the vector technique,
which had been used before in mice but never in primates.

Because it can be used to target specific genes in specific
parts of the brain, the technique could become a valuable
tool in brain research, said Mortimer Mishkin, an NIH
neuroscientist who was not part of the study.

"And it's temporary, which is a huge advantage, because you
can look both before and after," he said.