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Pediatric Use of ADHD Drug may Affect Developing Brain

The use of Ritalin, a stimulant similar to amphetamine and cocaine which is one of the most prescribed drugs for the attention deficit/hyperactivity disorder (ADHD), by young children may cause long-term changes in the developing brains, according to a study of mice by researchers at Weill Cornell Medical College in New York City.

"The changes we saw in the brains of treated rats occurred in areas strongly linked to higher executive functioning, addiction and appetite, social relationships and stress. These alterations gradually disappeared over time once the rats no longer received the drug," notes the study's senior author Dr. Teresa Milner, Professor of Neuroscience at Weill Cornell Medical College.

She suggests that doctors must exercise a lot of care as they diagnose ADHD and before prescribing Ritalin because the brain changes noted in the study though might be helpful in battling the behaviour disorder, can prove harmful if the drug is given to youngsters with healthy brain chemistry.

In the course of study, published in the Journal of Neuroscience, the researchers injected week-old male rat pups with Ritalin twice a day during their more physically active night-time phase. The animals continued receiving the injections up until they were 35 days old.

"Relative to human lifespan, this would correspond to very early stages of brain development. That's earlier than the age at which most children now receive Ritalin, although there are clinical studies underway that are testing the drug in 2- and 3-year olds," explains Jason Gray, a graduate student in the Program of Neuroscience and lead author of the study.

The researchers first looked at behavioural changes in the treated rats, and discovered that Ritalin use was linked to a decline in weight. In the "elevated-plus maze" and "open field" tests, rats examined in adulthood three months after discontinuing the drug displayed fewer signs of an xiety compared to untreated rodents.

"That was a bit of a surprise because we thought a stimulant might cause the rats to behave in a more anxious manner," Dr. Milner says.

The researchers also used high-tech methods to track changes in both the chemical neuroanatomy and structure of the treated rats' brains at postnatal day 35, which is roughly equivalent to the adolescent period.

"These brain tissue findings revealed Ritalin-associated changes in four main areas. First, we noticed alterations in brain chemicals such as catecholamines and norepinephrine in the rats' prefrontal cortex a part of the mammalian brain responsible for higher executive thinking and decision-making. There were also significant changes in catecholamine function in the hippocampus, a center for memory and learning," Dr. Milner says.

The researchers also saw treatment-linked alterations in striatum, a brain region known to be key to motor function, and in the hypothalamus, a centre for appetite, arousal and addictive behaviours.

Three months after the rats had stopped receiving Ritalin, the animals' neurochemistry largely resolved back to the pre-treatment state.

"That's encouraging, and supports the notion that this drug therapy may be best used over a relatively short period of time, to be replaced or supplemented with behavioural therapy," Dr. Milner says.

Dr. Milner, however, admits that it is too early to say whether the changes noted in the Ritalin-exposed brain will be of either benefit or harm to humans.

"One thing to remember is that these young animals had normal, healthy brains. In ADHD-affected brains where the neurochemistry is already somewhat awry or the brain might be developing too fast these changes might help 'reset' that balance in a healthy way. On the other hand, in brains without ADHD, Ritalin might have a more negative effect. We just don't know yet," she says.

"We're concerned about longer-term use. It's unclear from this study whether Ritalin might leave more lasting changes, especially if treatment were to continue for years. In that case, it is possible that chronic use of the drug would alter brain chemistry and behavior well into adulthood," she adds.


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