Ritalin Blues

Researchers discover that young rats given the stimulant Ritalin are more likely to develop the rodent equivalent of depression. These results could change the focus of depression research towards the neurotransmitter dopamine instead of serotonin.

By Carlin Flora, published on December 12, 2003 - last reviewed on June 17, 2005

Researchers discovered that young rats given the stimulant
Ritalin, the most common treatment for attention deficit hyperactivity
disorder, are more likely to develop the rodent equivalent of depression.
The finding raises new concerns about the widely prescribed drug and also
bolsters the idea that the neurotransmitter dopamine may play an
important role in both ADHD and depression in humans.

In ADHD, thought to affect between 3 and 5 percent of school-age
children in the U.S., kids have trouble paying attention and cannot control
their impulsive behavior. Diagnoses of the disease—and
prescriptions for Ritalin—have climbed quickly in recent years.
More than 2 million American children are currently diagnosed with ADHD,
according to the National Institute on Drug Abuse. Yet few studies of the
long-term effects of Ritalin on human children have been

In order to explore the relationship between cocaine addiction and
Ritalin, William Carlezon, psychologist and director of McLean
Hospital’s Behavioral Genetics Laboratory in Belmont, MA, and his
colleague Susan Andersen studied how the stimulant changes the developing
nervous system. They gave Ritalin to young rats for a period of time
roughly equivalent to human development from age 4 to 12. As adults,
these rats were much more likely to exhibit “learned
helplessness,” the rodent behavior that psychologists think is much
like human depression.

“No one can say for sure whether a rat is depressed,”
Carlezon says. “But when we gave them a stress test, they gave up
much faster than other rats.” Their lack of determination is
thought to be something like the despair felt by human sufferers of

The depressive rats were also less interested in cocaine than are
normal lab rats, which led researchers to believe that the brain systems
involving dopamine are at the root of both a tendency toward depression
and an aversion to cocaine. In a young brain, they theorize, Ritalin
disrupts the developing “reward” system.

“When we turn up the volume of the chemical dopamine by
administering Ritalin,” Carlezon says, “the synapses that are
forming disappear, and the ones still growing are cemented into
place.” As a result, the rats grow up with a half-baked reward and
pleasure system.

This theory points to a new direction in depression research.
Previous studies have typically emphasized serotonin, the brain chemical
influenced by drugs like Prozac. Carlezon now thinks that the
dopaminergic system plays a larger role in depression than previously
thought. “Both Ritalin and cocaine are more strongly linked to
dopamine transporters than to serotonin transporters,” he explains.
Inability to experience pleasure is a common symptom of

Nonetheless, it’s dangerous to leap from baby rats to young
humans when interpreting the results of the study, Carlezon warns.
Because rats don’t develop ADHD, the experiment doesn’t
necessarily shed much light on children with the disorder.

Nora Volkow, director of the National Institute on Drug Abuse,
developed the theory that children with ADHD have too little dopamine in
their brains. Ritalin works, she theorizes, because it “cleans
up” the molecules that get rid of dopamine. In other words, it
functions as a dopamine “reuptake inhibitor.”

Volkow agrees that further research of the long-term effects of
Ritalin is necessary. “But we don’t want parents or doctors
to panic, because that will do more damage than help,” she says.
Parents of children with ADHD must weigh the risks against the
consequences of not treating their child.