Ritalin and the Activity of Neurons

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Ritalin and the Activity of Neurons

Jim Windell

            Methylphenidate – better known by its brand name Ritalin – was first prescribed to children in the 1940s. But it really came into its own in the 1960s and 70s when children diagnosed with ADHD were given doses of Ritalin to increase their attention, reduce impulsivity and smooth out hyperactivity.

            Today, given that there are several other medications used to treat ADHD, about one in 11 children in the U.S. are prescribed stimulants like Ritalin. Many adults also use Ritalin and other such drugs to focus their attention. A great many adults, perhaps one in five, use the ADHD drugs off-label – usually without serious side-effects.

            The safety and efficacy of Ritalin and other drugs used primarily to treat ADHD are well understood, but still there is plenty left to learn about how they work. To that end, researchers from the University of Pittsburgh have studied how Ritalin affects activity in the brains of animals. Their intent is to provide a deeper understanding of how groups of brain cells govern attention.

           In previous research studies led by the University of Pittsburgh postdoctoral researcher Amy Ni, a link was found between how well animals did on a visual task and a particular measurement of neurons in the visual cortex. Specifically, it was shown in previous studies how likely they are to fire off independent of one another – as opposed to being synched up.

           In the current work, Ni and her colleagues found that animals that had taken methylphenidate performed better on a visual task of attention, and that the improvement happened exactly when that same metric of neuron activity shifted. The results of the Ni-led research was recently published in the journal Proceedings of the National Academy of Sciences.

           The researchers expected some of the study’s results based on what was already known about the drug. In the study, three animals took methylphenidate or a placebo on alternating days for two weeks of tests. On days when they took the drug, they spent longer on the task and performed better at it, but only when the required task occurred in a spot they were already paying attention to.

           In most neuroscience experiments, researchers target very small groups of neurons with electricity or light. “We definitely didn’t do that — we took these drugs, mixed them in fruit juice and gave them to the animals,” said Marlene Cohen, senior study author and professor of neuroscience in the Kenneth P. Dietrich School of Arts and Sciences. “It surprised me that a very general manipulation would have a very specific behavioral effect.”

           Along with learning more about how the drug works, such experiments allow researchers to gain a broader understanding of how patterns of firing neurons translate into behaviors like paying attention to what we see. By comparing how neurons act when the brain is in different states — such as when a subject has taken a drug versus when they haven’t — researchers can create more complete and useful models of how brain cells and behavior are linked.

           Dr. Cohen said that this is an approach that has not received much attention. This due in part to a lack of ways to fund research on how drugs change the activity of neurons. Cohen points out that this makes it difficult to look for “crossover treatments.”  Crossover treatments refer to novel uses for drugs that are already on the market.

           For now, though, this study remains an important first step in a line of research Cohen hopes to see far more of; that is, research that tries to connect the dots between the neural underpinnings of our behavior and how drugs affect it.

           “It’s one test case, and I think there’s a lot more to be done,” Cohen says. “I hope that people will see that these approaches are important.”

            To read the original article, find it with this reference:

Ni, A.M, Bowes, B.S., Ruff, D.A. & Cohen, M.R. (2022). Methylphenidate as a causal test of translational and basic neural coding hypotheses. Proceedings of the National Academy of Sciences,119(17),e2120529119; doi: 10.1073/pnas.2120529119.  



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