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University scientists discover link between glutamate, mood

New study shows increase in glutamate from ADHD medications results in elevated mood

In an attempt to understand the effects that drugs like Adderall have on typical brains, scientists have found a relationship between activity of the neurotransmitter glutamate and mood for the first time, according to a study conducted by University researchers.

“Considering the rising prevalence of off-prescription use of ADHD medications as study aids, especially on college campuses, it is crucial that we understand how these substances affect the healthy human brain,” said Adam Nitenson GS, co-author of the study. The study focused on psychostimulants that are commonly abused to enhance memory and learning.

Glutamate has been widely studied in recent years since the advent of more exact measuring techniques, said George Rebec, professor of psychology and brain sciences at Indiana University. “Thirty years ago, the main transmitters everyone talked about were dopamine, serotonin and norepinephrine because they were relatively easy to measure.”

Glutamate, “the brain’s principal excitatory neurotransmitter” is involved with processes relating to learning and memory, said Lisa Weyandt, professor of psychology and neuroscience at the University of Rhode Island. 

While “all addictive substances result in an increase in dopamine,” scientists currently do not understand how other neurotransmitters like glutamate can contribute to mood and addiction, Weyandt said. “It doesn’t make sense that if you affect one neurotransmitter system, another wouldn’t be involved in some way as well.”

Because “glutamate is important for driving a lot of motivated behaviors and goal-directed behaviors,” it can play a role in craving food or seeking the drug itself, Rebec said.

After administering a psychostimulant, researchers observed an increase in the presence of glutamate, measured through the use of a technique called magnetic resonance spectroscopy. The researchers tested two psychostimulants, both of which were ADHD drugs.

Furthermore, positive mood consistently followed glutamate production, according to the study. Women seemed to show a greater increase in glutamate response when compared with men, “indicating a heightened vulnerability to psychostimulants in females,” according to the study.

Because glutamate plays a major role in many brain processes, its potential effect on mood is unsurprising, Rebec said.

The study, however, did not speak to the cognitive effects of this glutamate increase, Weyandt said. It remains uncertain if this increase in glutamate translates into better planning or executive function, she added.

“It does appear that in healthy brains, there is a small effect for Adderall improving memory, but this is not found in all studies,” Weyandt said. Future research could help determine whether quality of work is actually being improved or if the drugs simply allow users to maintain attention for longer, she added.

In a previous study with ADHD subjects, glutamate increase was shown to last for a two-month medication period. This study observed non-ADHD subjects for only five hours, so long-term effects of the increase still need to be studied, Weyandt said.

“Kids may take these drugs early on, but what happens 20 years later, … that’s important research that, I think, still needs to be done,” Rebec said.  “We are still just scratching the surface of glutamate.”

Beyond opening questions for further research, the study offers a potential clinical application that takes advantage of the glutamate-mood link. “Maybe we could deal with a drug abuse problem by manipulating the receptors that respond to glutamate,” Rebec said.


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