Dopamine, learning and motivation: Why does this molecule drive our life forward?
Remember Pavlov and his dogs? This researcher, who left theology for medicine and physiology, conducted repeated pairings in which an initially neutral stimulus, such as a bell, accompanied the dogs’ food. He observed that after such training, the animals salivated at the sound of the bell, even if presented with no food.
Conditioning was born, with important implications for the development of behaviourism. The conditioned response, which is a type of learning, represents a nice example to understand how and why many species use experience to learn and to predict reward. And yes, more or less consciously, we are constantly predicting and 'hunting' rewards.
The brain needs rewards to learn, and those can be both external and internal. Social recognition or a salary rise may do the trick for the first. But when it comes to the inside, the dopaminergic system is responsible for providing joy. It works by releasing dopamine, which in humans gives us a sense of satisfaction and well-being, driving us forward in our daily lives. Our brain needs to modulate and restore the levels of this substance to feel motivated and move on.
Dopamine is a small molecule that ranks among the major neurotransmitters of the nervous system. It is present in both vertebrates and invertebrates and is popularly known as the happiness hormone. That may be an unemotional way of looking at it, but it turns out that we get through life because of it.
How does dopamine work in our brain?
A beautiful way to understand how dopamine works is to look at its wiring in the brain. Most of the neurons that secrete dopamine lay in the midbrain -the central part of the brain- and form three cell groups in three regions: the substantia nigra, the ventral tegmental area, and the retrorubral nucleus.
The groups of cells are contiguous, with no clear boundaries. From these small areas, dopaminergic neurons send generalised, ascending axonal projections to regions of the midbrain, finally reaching the frontal cortex. There is a large bunch of connections to the frontal cortex, responsible among other functions for decision-making.
Dopaminergic nuclei. “Ventral Tegmental Area” by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC BY-NC-SA) 4.0 International Licence.
The dopaminergic pathways. “Mesolimbic and Mesocortical Pathways” by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC BY-NC-SA) 4.0 International Licence.
Let’s now try to understand the biological meaning of dopamine by experiencing it: let’s think, for a moment, about a situation in our immediate past that made us feel good. We can feel the effect of dopamine in this instant of evocation. For example, a recall of feeling satisfied after completing a tricky task, or a small moment of heightened well-being when we get terrific news, instantly feels nice. Or the brief personal eureka we had in the biology class, when we understood something new, almost like an epiphany, works too. We could link this to a rapid release of dopamine. Likewise, we also know that this kind of pleasure is transient; this is one of the great mysteries: life tends to go through moments of greater and lesser well-being. But there is another way how dopamine works, generally present in the brain, which allows us to travel forward in life at cruising speed: a more sustained low-level release.
Although there is still much debate about the mechanisms underlying these two types of behaviour of the dopaminergic system, they seem to be related to two ways of neuronal neurotransmitter release durations:
(i) on one side, these neurons discharge dopamine very rapidly and briefly, namely phasic release -i.e. in a matter of a few seconds-.
(ii) on the other side, they may do so in a slower or tonic way, which means that the dopamine release lasts for several minutes.
Evidence is still emerging to link these two mechanisms to different roles of dopamine:
(i) learning reinforcement could correspond to a phasic discharge, just like Pavlov's dogs salivating at the sound of the bell and getting the food;
(ii) motivation to achieve a goal, which would keep us moving, perhaps is linked to a tonic discharge.
Our brain makes decisions based on emotions. Some of them are pleasure and well-being. Fear or anger are also emotions capable of making us learn and make decisions, the kind that involves movement, unlike sadness or disappointment, which involve still reactions. Once we recognize emotions that make us decide things in life, and the brain's preference for pleasure, we may wonder in what ways do we seek it. We know from neuroeconomics studies that if someone is offered 50 euros immediately or 55 after a few weeks, most people would choose 50. We tend to prefer a reward in a short time.
But despite the prize of achieving something with effort and time being much higher and long-lasting, our brain needs to find other bonuses along the way. They help to put our motivation at the right level and keep us going to achieve our goals in the mid and long terms. Many of the goals we set in life bring paths that are often uphill -I remember my PhD student years in this regard- where we need all the strategies we have on hand to reach the end. We sometimes abandon them as unsatisfactory. But they fill us with great experiences because that is how we learn, by trial and error.
Experiential learning, memory, and dopamine
Experts have found that we achieve learning and the experience that comes with it by trial and error. If you don’t try, you won’t fail. But failing is part of the process. Along the way, we get our prizes, or avoid punishment, at best. This process reinforces decisions we took, so we'll take them again, and -hopefully- we will learn through a positive outcome. To do it again. Because the brain vampirically seeks dopamine, and so over and over again. This representation looks at learning from an empirical point of view, although others may arise from cognitive psychology and didactics, extending the definition. Undoubtedly, we learn to make better decisions, which are those that favour our survival. In our societal contexts, this may eventually mean pursuing our well-being.
But how do we manage to make decisions? For a clue, we need to go back to the field of neuroeconomics: the brain constantly makes predictions of what the reward will be, just like deciding whether to go after it or not, depending on whether the reward is high or fast enough to set us in motion. In this way, we can understand the system as the one that gets us going through life, in which we seek well-being and pleasure in different ways to keep us motivated and going. Let’s look at the opposite: when the system is impaired, or we do not find motivation, we have the feeling of being stopped. And everything we learn that our brain feels fit for survival, we back up through memory, where dopamine again plays a key role.
To understand the role of dopamine in learning and memory, we can take an experiment published in 2004 by Richard Palmiter and his collaborators in Washington. These researchers injected dopamine into half of a group of dopamine-deficient mice, leaving the other half without. They set the mice to learn a task consisting of escaping from a water container through an exit platform. Given that mice are great swimmers, and without generating a big surprise or unexpected outcome, the group injected with dopamine managed to learn the task with success. The second group only succeeded after several attempts and with much lower performance rates than the injected group.
Going from mice to humans -which may not always be straightforward- we can draw two key insights from this study: one is that when dopamine is not present during the learning process, performance outcomes will be lower due to a lack of motivation. The other lies in the fact that dopamine also relates to memory. For learning to be consolidated, it needs storage in memory. Therefore, the presence of this molecule triggers the brain's mechanisms for remembering something, thus linking dopamine to the retention of learning.
What happens when this system does not work?
Several diseases in the brain are related to dopamine. For example, in elderly Parkinson's, the dopamine-secreting neurons in the substantia nigra progressively degenerate until the brain reaches low levels of the neurotransmitter, eventually leading to depression and cognitive deficits. Schizophrenia and bipolar disorder also have this molecule at the core of their mechanisms of functioning, according to our knowledge so far. Perhaps the paradigmatic situation and one of the most widespread is the case of addictions.
Far from being considered a moral or willpower problem, the biological vision offers a framework in which we can understand addiction beyond this. What is happening here is a change in the brain's functional mechanisms, which is quite costly to redirect -as people who have experienced it know well- requiring more than good intentions to overcome.
“A common misperception is that addiction is a choice or a moral issue, and all you have to do is stop. But nothing could be further from the truth,” says Dr George Koob, director of the NIH's National Institute on Alcohol Abuse and Alcoholism. “The brain changes with addiction, and it takes a lot of work to get it back to normal. The more drugs or alcohol you have taken, the more damaging it is to the brain.”
Experts explain that addiction hijacks the dopaminergic system. We can figure it out as the following: if your brain is healthy and cared for, it reinforces healthy behaviours, because these learned habits and behaviours generate pleasure. On the other hand, in situations of discomfort or danger, a healthy brain pushes the body to react quickly with fear or alarm, to get out of danger. It is at this moment of risk that we are tempted to decide to engage in avoidance behaviour, such as taking a drug or buying something expensive without assessing what the consequences might be. This also generates pleasure in the very short term. Because it involves dopamine and a benefit from the avoidance of danger due to the sensation of pleasure, the behaviour begins to reinforce.
When the person also becomes addicted to a substance, that is, when the behaviour becomes abusive, the normal wiring of useful brain processes may begin to work against them. Drugs or alcohol can hijack the pleasure and reward circuits in the brain and make you want more and more. Addiction can also cause the emotional circuits of danger detection to speed up, making the person feel anxiety and stress when they are not taking the substance they are addicted to. At this point, people use drugs or alcohol so that they don’t feel bad, and not for pleasure, progressively killing the inner drive.
Is dopamine only in the brain?
There is a recent line of evidence that dopamine, besides the brain, is also present in the rest of the body. In recent years researchers studied the so-called gut-brain axis. They localised a cluster of more than 200 million neurons in the gut, known as the second brain. Technically called the enteric nervous system, it appears to work independently of the central nervous system, which includes the brain and the spinal cord. One of the features of this second brain is that it contains numerous neurons that produce the molecule. Research estimates that the gut generates around 50% of the body's dopamine, in addition to 95% of serotonin, another neurotransmitter linked to well-being.
Surprisingly, some recent research has linked the state of our gut and its microbiome -the bacterial population- to different mental states, and even brain diseases. This line of thinking raises a whole series of implications: for example, would this mean that depending on the microbial gut flora we can suffer from mental illness? And, is this directly linked to the type of food we eat? It would also be interesting to know what treatments can be implemented based on this line of evidence.
In a review paper published in 2021 by Yu Chen and co-workers in China, they suggest that so-called microbial therapy, focused on restoring microbiota, could be effective in certain illnesses. We will have to wait for the field to advance to see how it can help regulate neurotransmitter levels in the brain, for example in situations of depression, or to prevent the onset of a disorder. It is always a good idea to maintain a balanced diet to the body's needs, though.
One of the questions that remains open is how this intestinal dopamine can reach the brain by crossing the so-called blood-brain barrier. As far as research shows, the chemical nature of dopamine makes it impenetrable to the brain from the outside bloodstream. There are also questions relating to what dopamine does in the gut. Does the same thing in the body as it does in the brain, and does it work also as a reward system? Research also shows that this second brain also performs complex calculations like the main one. Is then the gut involved in learning or making decisions? These ideas suggest we may start thinking about wellness from a bodily perspective: maybe the mystery of feeling good, and perhaps of the body's learning mechanisms, is not only contained in the brain.
Father of medicine Hippocrates of Kos, who drew up the famous Hippocratic Oath in the 3rd-4th century BC, said “May food be your nourishment and food be your medicine”.
However, as one gut bacterium said to another, “It is very dark out there”.
To know more
Wise, R. Dopamine, learning and motivation. Nat Rev Neurosci 2004, 5, 483–494. doi: 10.1038/nrn1406
Wright M., Walsh J.J., Lewis E.M., Luo L., Deisseroth K., Dölen G., Malenka R.C.. Gating of social reward by oxytocin in the ventral tegmental area. Science 2017, Sep 29;357(6358):1406-1411. doi: 10.1126/science.aan4994.
Denenberg, Victor H., Douglas S. Kim, and Richard D. Palmiter. "The role of dopamine in learning, memory, and performance of a water escape task." Behavioural brain research 2004, 148.1-2: 73-78. doi: 10.1016/S0166-4328(03)00183-9
Chen, Y., Xu, J., Chen, Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients 2021, 13, 2099. doi: 10.3390/nu13062099
Daniel Lieberman. Dopamine: Driving Your Brain into the Future. TED Talk
