Dec. 8, 2003 -- Ritalin use in preteen children may lead to depression later in life, studies of rats suggest.

It's an open question whether what passes for depression in lab rats has anything to do with depression in humans. But early use of Ritalin and other stimulant drugs seems to permanently alter animals' brains. That raises concerns that the same thing might be happening in children who take these drugs for attention deficit hyperactivity disorder (ADHD).

The findings come from a research team led by William A. Carlezon Jr., PhD, director of the behavioral genetics laboratory at McLean Hospital and associate professor at Harvard Medical School. The study appears in the Dec. 15 issue of Biological Psychiatry.

"Rats exposed to Ritalin as juveniles showed large increases in learned-helplessness behavior during adulthood, suggesting a tendency toward depression," Carlezon says in a news release. "These rats also showed abnormally high levels of activity in familiar environments. [This] might reflect basic alterations in the way rats pay attention to their surroundings."

Ritalin, Cocaine, and the Brain

Ritalin and cocaine have different effects on humans. But their effects on the brain are very similar. When given to preteen rats, both drugs cause long-term changes in behavior.

One of the changes seems good. Early exposure to Ritalin makes rats less responsive to the rewarding effects of cocaine. But that's not all good. It might mean that the drug short-circuits the brain's reward system. That would make it difficult to experience pleasure -- a "hallmark symptom of depression," Carlezon and colleagues note.

The other change seems all bad. Early exposure to Ritalin increases rats' depressive-like responses in a stress test.

"These experiments suggest that preadolescent exposure to [Ritalin] in rats causes numerous complex behavioral adaptations, each of which endures into adulthood," Carlezon and colleagues conclude. "This work highlights the importance of a more thorough understanding of the enduring neurobiological effects of juvenile exposure to psychotropic drugs."