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Sunday, March 03, 2024
ADHD monkey

Monkeys may be future model for Ritalin-ADHD studies

Impulsivity —a tendency to act without forethought—is one of the defining characteristics of Attention Deficit Hyperactivity Disorder, or ADHD. Impulsive people struggle with waiting for rewards, or taking delayed gratification. Thus, they have trouble successfully setting and achieving long-term goals.

Helping impulsive people succeed in life has become a main concern of scientists as the levels of children diagnosed with ADHD has risen—up to 11 percent for people between the ages of four and 17.

Therefore, associate professor of neuroscience Luis Populin and graduate student Abigail Zdrale Rajala studied impulsive behavior in two rhesus monkeys —one which was very calm, and one which was impulsive. The monkeys were given a choice of two pictures, one that resulted in the monkey receiving a small reward immediately, and one that resulted in the monkey getting a larger reward after a wait of about 16 seconds.

The calm monkey repeatedly chose the larger reward with the longer wait, while the impulsive monkey chose immediate gratification.

There is not yet a monkey model for ADHD.

“But they [monkeys] exhibit behaviors similar to those seen in people with ADHD under similar circumstances,” Populin said.

Monkeys can’t tell us what they are thinking or feeling. But by establishing that one monkey can be more impulsive than another, scientists can isolate and test this symptom of ADHD. Then it will be possible to extrapolate the results to humans.

Following the initial test, Populin and Rajala gave the impulsive monkey a low dose of methylphenidate—the active ingredient in the common ADHD drug Ritalin. The monkey changed his impulsive ways, and often chose to wait for the larger reward.

Methylphenidate affects the brain’s supply of dopamine, a neurotransmitter that affects motivation, behavior, thought, feeling and rewards. People with ADHD show signs of dopamine shortage, although the root cause isn’t clear. They might be using up their dopamine supplies faster than a “normal” person. Or they could have less dopamine to begin with.

Methylphenidate blocks the “re-uptake” of dopamine, keeping it available for longer periods of time. People on low doses of methylphenidate are calmer, more attentive, and less impulsive. This information can offer a window into the origin of ADHD.

“We don’t know exactly what the cause of ADHD is, it’s something that’s under contention,” Rajala said.

There are multiple hypotheses among neuroscientists and psychologists. One group believes that ADHD is caused by dysfunction in the prefrontal cortex, the area of the brain that controls rational thought. Another group thinks that a flaw in the reward-processing system is to blame.

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The majority of dopamine cells are found in the brain stem, an area that controls many unconscious functions of the brain, including reward-processing. Some scientists say the rewards center must cause ADHD because methylphenidate operates on dopamine cells, and dopamine cells reside in the brain stem. The effectiveness of methylphenidate in changing rewards preferences in monkeys gives further evidence to this hypothesis.

But simply using methylphenidate isn’t enough.

“It may not be what you give, but how much you give,” Rajala said.

The dosing required for ADHD drugs is poorly understood—it varies from person to person because the brain is so complicated. Too much methylphenidate can inhibit cognitive function, too little methylphenidate may not effectively treat ADHD. Experimental work is required to discern the factors that determine how much drug needs to be used.

But people aren’t easily experimented on. Parents want what’s best for their children, and having a doctor play around with a child’s daily dose of methylphenidate isn’t best. Doctors must give what is to their knowledge the best dose, and can observe the effects from there.

Monkeys don’t have to drive a car, ace their next history test or make difficult career choices, so they offer a bit more room to test doses of ADHD drugs. Additionally, variables are more easily controlled in monkeys because they have simpler lives than people. While scientists are still limited in in how they can experiment on monkeys, the model could open many doors.

Work on monkeys may eventually lead to better treatment of people with ADHD. Ideally, scientists and doctors would be able to determine the required doses of ADHD drugs with precision by gaining a better understanding of the mechanisms and effects of drugs like methylphenidate.

Hopefully, scientists will be able to stop impulsivity from limiting the potential of any person.

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