Summary: Higher levels of glutathione in the nucleus accumbens correlated with better and more consistent performance on motivation-based tasks. The findings suggest that improvements in accumbal antioxidant function that can be acquired through diet or supplementation may be a feasible approach to help increase motivation.
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In life, motivation can be the difference between success and failure, goal setting and goallessness, well-being and unhappiness. And yet, getting and staying motivated is often the most difficult step, a problem that has given rise to much research.
A very small part of that research has focused on the question of metabolism. “Do differences in metabolites in the brain affect our ability to motivate?” asks Professor Carmen Sandi at EPFL’s School of Life Sciences. “If that’s the case, could nutritional interventions that can affect metabolite levels be an effective vehicle for improving motivated performance?”
Sandi’s group, with colleagues at the Nestlé Institute of Health Sciences, has now published a study that sheds the first light on answering that question. The researchers focused on a deep area of the brain called the nucleus accumbens, which is known to play an important role in regulating functions such as reward, reinforcement, aversion and, not least, motivation.
Metabolism and oxidative stress in the brain
The idea behind the study was that the brain itself, like all the tissues in our body, is subject to constant oxidative stress as a result of its metabolism.
What is oxidative stress? As cells “eat” various molecules for fuel, they produce a series of toxic waste products in the form of highly reactive molecules known collectively as “oxidative species.” Of course, cells have a number of mechanisms to remove oxidative species, restoring the chemical balance of the cell. But that battle continues, sometimes that balance is disturbed and that disturbance is what we call “oxidative stress”.
The Glutathione Connection
So the brain is often subject to excessive oxidative stress due to its neurometabolic processes, and the researchers’ question was whether antioxidant levels in the nucleus accumbens can affect motivation. To answer the question, the scientists looked at the brain’s most important antioxidant, a protein called glutathione (GSH), and its relationship to motivation.
“We evaluated the relationships between metabolites in the nucleus accumbens, a key brain region, and motivated performance,” says Sandi. “We then turned to animals to understand the mechanism and test causality between the metabolite found and performance, also showing that nutritional interventions modify behavior through this pathway.”
GSH tracking in the nucleus accumbens
First, they used a technique called “proton magnetic resonance spectroscopy,” which can assess and quantify the biochemistry in a specific region of the brain in a non-invasive way.
The researchers applied the technique to the nucleus accumbens of humans and rats to measure GSH levels. They then compared those levels to how well or poorly their human and animal subjects performed on standardized effort-related tasks that measure motivation.
What they found was that higher levels of GSH in the nucleus accumbens correlated with consistently better performance on motivational tasks.
GSH levels and motivation
But correlation doesn’t imply causation, so the team turned to in vivo experiments with rats given microinjections of a GSH blocker, which downregulates the synthesis and levels of the antioxidant. The rats now showed less motivation, as seen in poorer performance on tests incentivized by effort-based rewards.
In contrast, when the researchers gave the rats a nutritional intervention with the GSH precursor N-acetylcysteine, which increased GSH levels in the nucleus accumbens, the animals performed better. The effect was “potentially mediated by a cell-type-specific change in glutamatergic inputs to accumbal medium spiny neurons,” as the authors write.
Can nutrition or supplements help motivation?
“Our study provides new insights into how brain metabolism is related to behavior and presents nutritional interventions targeting the key oxidative process as ideal interventions to facilitate exertional endurance,” the authors conclude. The study’s findings “suggest that enhancing accumbal antioxidant function may be a feasible approach to increasing motivation.”
“N-acetylcysteine, the nutritional supplement we gave in our study, can also be synthesized in the body from its precursor, cysteine,” says Sandi. “Cysteine is found in ‘high-protein foods,’ such as meat, poultry, fish, or shellfish. Other sources with lower content are eggs, whole foods such as bread and cereals, and some vegetables such as broccoli, onions and legumes.
“Of course, there are other ways beyond N-acetylcysteine to increase GSH levels in the body, but how these relate to levels in the brain, and particularly the nucleus accumbens, is largely unknown. Our study represents proof of principle that dietary N-acetylcysteine can increase GSH levels in the brain and facilitate exertional behavior.”
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About this research news in motivation and neuroscience
Author: press office
Font: EPFL
Contact: Press Office – EPFL
Image: The image is in the public domain.
original research: Open access.
“Glutathione in the nucleus accumbens regulates motivation to exert reward-incentivized effort”, by Ioannis Zalachoras et al. eLife
Summary
Glutathione in the nucleus accumbens regulates motivation to exert reward-incentivized effort
Emerging evidence is implicating mitochondrial function and metabolism in the nucleus accumbens in motivated performance.
However, the brain is vulnerable to excessive oxidative insults resulting from neurometabolic processes, and it is unknown whether antioxidant levels in the nucleus accumbens contribute to motivated performance.
Here, we identify a critical role for glutathione (GSH), the brain’s most important endogenous antioxidant, in motivation.
Using proton magnetic resonance spectroscopy (1H-MRS) in ultra-high field in clinical and preclinical populations, we establish that higher accumbal GSH levels are highly predictive of better and particularly stable performance over time on effort-related tasks.
Causality was established in preclinical in vivo experiments that first demonstrated that downregulation of GSH levels via microinjections of the GSH synthesis inhibitor butionine sulfoximine into the nucleus accumbens impaired performance-driven performance. effort-based reward.
Furthermore, systemic treatment with the GSH precursor N-acetyl-cysteine (NAC) increased accumbal GSH levels and led to improved performance, potentially mediated by a cell-type-specific change in glutamatergic inputs to accumbal medium spiny neurons. . Our data indicate a close association between accumbal GSH levels and the individual’s ability to exert reward-incentivized effort over time.
They also suggest that enhancing accumbal antioxidant function may be a feasible approach to increasing motivation.
