The November sun was shining through the glass roof, making moving shadows that lit up the shallow end of the swimming pool. I was doing a few laps, thoroughly enjoying my afternoon at the local rec center. I wondered, why is it that exercise makes me feel good?
Over the last two decades, much of the research on the neural basis of reward has focused on dopamine, a neurotransmitter that is released by a relatively small number of neurons in the midbrain, and sent to pretty much all the rest of the brain and other organs. When an animal sees something that it likes, for example food, these neurons in the midbrain release dopamine. The magnitude of the release is related to the subjective value of the rewarding stimulus. So when you see ice cream, your brain probably releases more dopamine than when you see broccoli.
However, when you have to work to acquire the rewarding item, then the magnitude of dopamine release becomes smaller as the required effort becomes larger. That is, if you have to run a mile to get the ice cream, then the broccoli may seem like a better choice. So it is puzzling that exercise, which basically involves generating a lot of effort, should result in an increase in the production of dopamine. But there is indeed some evidence for this.
In 1994, Satoshi Hattori, Makoto Naoi, and Hitoo Nishino in Nagoya, Japan trained 6 rats to run on a treadmill. After training, they measured dopamine levels via micro-dialysis in a region of the basal ganglia (striatum) at 20 minute intervals (this became the baseline measure of dopamine). They then had the animals run for 20 minutes at a slow, medium, or fast speed, re-measured dopamine levels during the run, and then each 20 minutes after completion of the run (for another 3 hours). They found that during the medium and fast runs, dopamine levels increased. Interestingly, dopamine levels remained elevated for about 1.5 hours after completion of the run (in the figure below, the x-axis has bins of 20 minute duration). As a result, the study demonstrated that dopamine levels increased with physical exercise, and remained elevated beyond completion of the exercise.
But this result was in rats. Does the same thing happen in humans? In 2000, Gene-Jack Wang, Nora Volkow and colleagues at State University of New York at Stony Brook asked 12 people who regularly exercised to participate in a PET study, where they used a scanning technique to indirectly measure dopamine levels in a region of the basal ganglia (striatum). They scanned the brain and measured dopamine levels at baseline, and then they had the volunteers run on a treadmill for 30 minutes. Following the run, they again scanned the brain. Surprisingly, they found no significant changes in dopamine levels (as shown in the figure below). In these people who exercised regularly, the run on the treadmill seemed to have had no particular effects on the dopamine levels.
Given the results in rats, this result in humans was puzzling, and to my knowledge still remains unresolved.
Fortunately, over the last decade there have been advances in our ability to directly record from dopamine neurons in the primate brain. With these recordings it is possible to see how dopamine responds to both reward and effort.
In 2015, Chiara Varazzani, Sebastian Bouret, and their colleagues in Paris, France, trained thirsty monkeys to squeeze a handle in order to receive juice. There were 3 juice amounts (small, medium, and large amounts of juice) and 3 amounts of effort (small, medium, and large amounts of force), producing a total of 9 conditions.
There was a symbol associated with each of the 9 conditions. For example, when the cue was a long, narrow rectangle, it meant that the monkey would have to squeeze the handle by a small amount to get a small amount of juice. When the cue was a circle, it meant that the monkey would have to squeeze by a large amount to get the same small amount of juice. In this way, the symbols defined both the amount of reward and the required effort. Once the symbol was removed, a “go” cue appeared, instructing the animal to actually produce the force. If the animal produced the right amount of force, it received the reward.
The authors recorded from 90 dopamine neurons in the substantia nigra, another region in the basal ganglia, and found that when the monkey saw the symbol indicating the reward and effort levels, the dopamine cells responded more with increasing reward. However, as the required effort increased, the dopamine response became smaller. Therefore, when the animal received information regarding effort and reward contingencies of the upcoming trial, it produced more dopamine if the trial was to include a large amount of juice, but less dopamine if the trial was to require a large amount of force. In a sense, dopamine acted like a sum of reward minus effort, signaling the value (or utility) of the upcoming event. At the time of cue, dopamine levels signaled how much the animal “liked” the following trial: the brain got more dopamine if the cue promised a lot of juice, and required only a small amount of effort.
Interestingly, during the time that the animal actually squeezed the handle and produced the required force, dopamine cells once again responded, but now with increased rates when the required force was larger (in the figure below, the x-axis is time, with each interval 200ms). That is, the same cells that earlier had reduced their discharge when told that the trial would involve a large amount of effort, now increased their discharge during the actual production of the large effort.
These results highlight the dual nature of dopamine. When the brain is deciding between two options that each promise some amount of reward, and require some amount of effort, dopamine response becomes larger with greater promised reward, and becomes smaller with greater required effort. Maybe this is why we tend to pick the more rewarding, less effortful option. However, when the brain is sending motor commands to actually perform the option that we selected, dopamine responds more with the increasing effort, and now seems impervious to the promised reward. Maybe this is why when we exercise, that is, when we spend effort, we tend to feel as if we are rewarded: because during exercise, dopamine makes effort seem like reward.
Satoshi Hattori, Makoto Naoi, and Hitoo Nishino (1994) Striatal dopamine turnover during treadmill running in the rat: relation to the speed of running. Brain Research Bulletin 35:41-49.
Chiara Varazzani, Aurore San-Galli, Sophie Gilardeau, and Sebastien Bouret (2015) Noradrenaline and dopamine neurons in the reward/effort trade-off: a direct electrophysiological comparison in behaving monkeys. Journal of Neuroscience 35:7866-7877.
Gene-Jack Wang, Nora D. Volkow, Joanna S. Fowler, et al. (2000) PET studies of the effects of aerobic exercise on human striatal dopamine release. Journal of Nuclear Medicine 41:1352-1356.