Dopamine

Zero Motivation to Exercise? Dopamine Receptors Could Be Why

Dysfunctional dopamine receptors are linked to inactivity in mice, study finds.

Posted Dec 30, 2016

Life Science Databases/Wikimedia Commons
The striatum (in red) is located in the basal ganglia. The striatum contains D2-type (D2R) Dopamine receptors which make physical movement rewarding and spark the initial motivation to voluntarily move your body.
Source: Life Science Databases/Wikimedia Commons

Chronically inactive mice who eat an unhealthy diet and become obese display very little motivation to move their bodies according to a new report from the National Institute of Health (NIH) published online yesterday in the journal Cell Metabolism.

Interestingly, the researchers believe that the lack of motivation to move stems primarily from malleable alterations in D2-type (D2R) dopamine binding receptors in the striatum of the basal ganglia—not simply from being overweight or lacking willpower.

Although this is an animal study, these groundbreaking findings are a follow-up to similar human research conducted earlier this year at the NIH. The initial study identified a correlative association between an impairment of dopaminergic pathways (which deliver the “reward molecule” dopamine to receptors) in the striatum and chronic inactivity.

Dopamine receptors in the striatum trigger feelings of reward that make your brain say "do it more." This helps to hardwire both positive lifestyle behaviors that become habits, as well as harmful addictions. In previous studies, malfunctions of the basal ganglia have been associated with Parkinson’s and Huntington’s diseases, autism spectrum disorders (ASD), obsessive-compulsive disorder (OCD), Tourette’s syndrome, and other neuropsychiatric disorders. 

Did You Make a New Year's Resolution to Sit Less, Exercise More, and Eat Better?

If you're like hundreds of millions of people around the globe...odds are that you'll make a New Year’s resolution to adopt healthier lifestyle habits in 2017.

Unfortunately, the chances of sticking with your exercise resolution long enough for moderate-to-vigorous physical activity (MVPA) to become a daily habit are statistically slim. But there is hope! Because of the neuroplasticity of your basal ganglia, the NIH researchers found that dopamine receptors are malleable and can be reshaped and rewired if you can stick with slight improvements to diet and exercise long enough to create an upward spiral within the striatal loop-circuit. This improves dopamine D2R binding and makes breaking a sweat feel good, which will make you want to exercise more.

Until recently, most experts would blame a lack of willpower as being the prime culprit for people failing to stay motivated to stick with a workout regimen. Now, for the first time, it appears that abnormalities within someone's D2R dopamine signaling rooted in the striatum of the basal ganglia may explain why some of us are more prone to be couch potatoes than others. 

All animals (including humans) seek pleasure and avoid pain. Without proper dopamine signaling, it’s impossible for exercise to feel like a pleasurable or rewarding experience. If your D2-type dopamine receptors are dysfunctional, it can make physical activity a very disagreeable experience on a neurobiological level. Although exercise creates "runner's high" for some, this research helps to explain why the link between exercise and feeling good isn't a universal phenomenon in a way that goes beyond endorphins or endocannabinoids. 

In a statement to Cell Press, the study's senior author Alexxai V. Kravitz, an investigator in the Eating and Addiction Section, Diabetes, Endocrinology, and Obesity Branch at the NIH said,

“In many cases, willpower is invoked as a way to modify behavior. But if we don't understand the underlying physical basis for that behavior, it's difficult to say that willpower alone can solve it.

We know that physical activity is linked to overall good health, but not much is known about why people or animals with obesity are less active. There's a common belief that obese animals don't move as much because carrying extra body weight is physically disabling. But our findings suggest that assumption doesn't explain the whole story.

Other studies have connected dopamine signaling defects to obesity, but most of them have looked at reward processing—how animals feel when they eat different foods. We looked at something simpler: dopamine is critical for movement, and obesity is associated with a lack of movement.”

Kravitz's other research focuses on basal ganglia circuits and how their function changes due to influences such as obesity, addiction, depression, and Parkinson's disease. 

When he began conducting obesity research a few years ago, Kravitz was surprised to discover similar patterns of movement behavior between obese mice and laboratory mice with Parkinson's disease. Based on this serendipitous observation, he hypothesized that the reason that both obese and Parkinsonian mice were inactive was due to dysfunction in their dopamine systems.

After analyzing six different components in the dopamine signaling pathways in laboratory animals, Kravitz and colleagues pinpointed that inactive, obese mice had deficits in the D2-type dopamine receptor but not the D1-type receptor. Although other factors are most likely involved in this process, the deficit in D2R is sufficient to explain the lack of activity in obese mice, the researchers concluded.

"Striosome-Dendron Bouquets" in the Basal Ganglia May Drive Voluntary Movement

The latest findings by Kravitz et al. on D2-type dopamine receptors and inactivity dovetail with research being conducted by MIT neuroscientists who pinpointed dopamine receptors in the striatum as being associated with decisions requiring a "cost-benefit analysis." I reported on these findings in a September 2016 Psychology Today blog post, "Study Pinpoints Brain Circuitry of Emotional Decision-Making." 

The MIT researchers used a revolutionary technique developed at the Massachusetts Institute of Technology known as “expansion microscopy” to zoom in on a direct communication pathway to the striatum that is directly linked to another complex dopamine-fueled subsystem in the basal ganglia.

The researchers coined this subsystem a “striosome-dendron bouquet.” The cluster of neurons in this bouquet are involved in making decisions that require any type of "cost-benefit analysis" in which you weigh the pros and cons of a potential decision using pragmatic rationale combined with a gut-feeling of the emotional toll linked to a specific choice. 

This study was led by Ann Graybiel, an Institute Professor at MIT and member of the McGovern Institute for Brain Research. In a statement to MIT, Graybiel said that the striosome-dendron bouquet may also be a potential target for treating the neural degeneration seen in Parkinson’s disease. Please take a few minutes to watch this YouTube video of Ann Graybiel describing her research on the basal ganglia at MIT.

If You Stick With It, Habitual Lifestyle Choices Can Reboot Your Dopamine Receptors

The latest discoveries on the ability of D2-type dopamine receptors to increase or decrease someone's motivation to move his or her body provide a neuroscience-based explanation as to why it's an uphill battle for some people to psychologically kickstart their motivation to be more physically active through sheer force of will.

Hopefully, this new empirical evidence will reduce moral judgments and any stigma people who may be overweight and avoid physical activity experience. The scientific evidence suggests that a lack of motivation to exercise has deep neurobiological roots and goes far beyond simply being "lazy." 

That said, the best news of the latest research from the NIH is that the dysfunction of the D2-type dopamine receptors is not set in stone. By gradually increasing physical activity, eating a healthier diet, and losing some weight—the basal ganglia seems to reboot and dopamine receptors ‘wake up.’ This kickstarts the biological reward mechanism that can make someone want to move his or her body voluntarily.

Future research by Kravitz and his team at the NIH will focus on how eating an unhealthy "obesogenic" diet affects dopamine signaling. The researchers also plan to examine how long it takes for obese mice to regain higher motivation levels and become active once they begin eating a healthier diet, moving more, and losing weight. Stay tuned!

References

Danielle M. Friend, Kavya Devarakonda, Timothy J. O'Neal, Miguel Skirzewski, Ioannis Papazoglou, Alanna R. Kaplan, Jeih-San Liow, Juen Guo, Sushil G. Rane, Marcelo Rubinstein, Veronica A. Alvarez, Kevin D. Hall, Alexxai V. Kravitz. Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity. Cell Metabolism, 2016; DOI: 10.1016/j.cmet.2016.12.001

Kravitz, A. V., O’Neal, T. J., & Friend, D. M. (2016). Do Dopaminergic Impairments Underlie Physical Inactivity in People with Obesity? Frontiers in Human Neuroscience, 10, 514. http://doi.org/10.3389/fnhum.2016.00514

Jill R. Crittenden, Paul W. Tillberg, Michael H. Riad, Yasuyuki Shima, Charles R. Gerfen, Jeffrey Curry, David E. Housman, Sacha B. Nelson, Edward S. Boyden,  and Ann M. Graybiel. Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons. PNAS 2016 113 (40) 11318-11323; published ahead of print September 19, 2016, doi:10.1073/pnas.1613337113