Gene therapy cures monkeys of laziness

Procrastinating primates can be turned into workaholics, thanks to gene therapy. The discovery, which sheds light on the workings of the brain's reward centre, may further our understanding of mood disorders, such as depression and obsessive-compulsive disorder.

Like many humans, monkeys tend to slack off when their goal is distant, then work harder as a deadline looms. But when a key gene is turned off, the primates work hard from the word go, researchers report in PNAS Online.

"The gene knockdown triggered a remarkable transformation in the simian work ethic," says Barry Richmond of the National Institute of Mental Health in Bethesda, Maryland, who studied the animals.

Richmond's team trained four monkeys to release a lever when a spot on a computer screen turned from red to green. The animals had to complete several trials correctly before they received a reward. To give them an idea of how many trials were left, a grey bar on the screen became progressively brighter as the task progressed.

The team then injected a short strand of DNA into each monkey's brains, temporarily switching off a key gene in a region of the brain called the rhinal cortex, which is known to be involved in processing reward signals. The gene encodes a protein called a D2 receptor that makes nerve cells more sensitive to dopamine, a chemical that is also implicated in the perception of reward.

With the gene turned off, the monkeys were unable to anticipate how many trials were left before the reward was given. They stopped procrastinating and worked hard throughout the task, making consistently fewer errors at every stage.

"The monkeys became extreme workaholics," says Richmond. "This was conspicuously out-of-character for these animals."

The team hope that their discovery will help researchers understand the brain mechanisms that underlie human mood disorders, where the perception of reward has gone awry.

Depressed people, for example, commonly fail to find work rewarding. Sufferers of obsessive-compulsive disorder and bipolar disorder (also known as manic depression) often work frantically, sometimes for little reward.

The study suggests that patients like this may have altered patterns of D2 receptor expression. Researchers can now test this hypothesis further in animal and human studies.