Saturday, July 05, 2008

Does Ritalin specifically target the prefrontal cortex?

I've long been impressed by the unexpected safety of Ritalin (methylphenidate). It's rare for a medication to both alter brain function and have low toxicity, yet many years of use have given us little bad news.

Now FP reports on a study that suggests why Ritalin is both safe and effective for ADHD. It might not the drug we thought it was ...
FuturePundit: Research On Ritalin Mechanism Of Action
... In a paper publishing online this week in Biological Psychiatry, University of Wisconsin-Madison psychology researchers David Devilbiss and Craig Berridge report that Ritalin fine-tunes the functioning of neurons in the prefrontal cortex (PFC) - a brain region involved in attention, decision-making and impulse control - while having few effects outside it.
... Mounting behavioral and neurochemical evidence suggests that clinically relevant doses of Ritalin primarily target the PFC, without affecting brain centers linked to over-arousal and addiction. In other words, Ritalin at low doses doesn't appear to act like a stimulant at all.
Ritalin at lower doses appears to cause the prefrontal cortex (PFC) to be more sensitive to signals coming in from the hippocampus.
When they listened to individual PFC neurons, the scientists found that while cognition-enhancing doses of Ritalin had little effect on spontaneous activity, the neurons' sensitivity to signals coming from the hippocampus increased dramatically. Under higher, stimulatory doses, on the other hand, PFC neurons stopped responding to incoming information. "This suggests that the therapeutic effects of Ritalin likely stem from this fine-tuning of PFC sensitivity," says Berridge. "You're improving the ability of these neurons to respond to behaviorally relevant signals, and that translates into better cognition, attention and working memory." Higher doses associated with drug abuse and cognitive impairment, in contrast, impair functioning of the PFC...
I wonder if this will change thoughts about optimal dosing of Ritalin. I would very much like to see animal models studied to look for tolerance of Ritalin's alleged PFC effects.

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