The Many Faces of Dopamine
The history of dopamine is full of experimental surprises and paradigmatic shifts. For many years after its discovery, it was thought dopamine’s only role in the brain was in the synthesis of norepinephrine, which is made from dopamine with the help of the enzyme dopamine B-hydroxylase. Around the middle of the twentieth century, however, it began to be recognized as having important physiological effects in its own right, and by the mid 1960s it was found that low levels of it were correlated with Parkinson’s disease. Continued investigation of dopamine led to the realization that it is a neurotransmitter, with its own receptors and pathways, and that its influence on brain activity is profound.
When a link between dopamine transmission and rewarding experiences (e.g. eating, sex, drugs) was established, it caused many to understandably hypothesize that dopamine was responsible for our subjective experience of pleasure. This is perhaps when dopamine reached the height of its stardom, as it began to garner media attention as the “pleasure transmitter”. Its role was readily embraced by a populace who were anxious to discover what exactly was behind their persuasive urge to sneak a piece of chocolate, pursue a one-night stand, or indulge in recreational drug use.
But science eventually caught up with the hype when researchers began to notice that dopamine didn’t correlate exactly with pleasure. For one thing, hedonic reactions could be sustained even after the administration of a dopamine antagonist (which inhibits dopamine’s effects). Additionally, dopamine transmission seemed to occur around the time a reward was being enjoyed, but not always during. For example, dopaminergic neurons might be activated as a person reaches for a piece of chocolate, but not while it is in their mouth, indicating more of an anticipatory role than an hedonic one.
It was eventually suggested that dopamine’s role is not in experiencing pleasure per se, but in making the association between an external stimulus and a rewarding experience. In this way, dopamine could act as a reinforcer, prompting associative learning that allows an organism to remember stimuli that proved to be rewarding in the past, and attribute importance, or salience, to them. Dopamine may be involved in the “wanting” aspect of pleasurable things, but not necessarily the “liking” of them.
So what causes pleasure, then? Leknes and Tracey, in April’s issue of Nature Reviews Neuroscience, summarize a current view of the neurobiological substrates of pleasure and pain. According to this perspective, dopamine is responsible for the motivation required to seek out a reward while endogenous opioid systems are accountable for our subjective experience of pleasure. Dopamine is needed for “wanting”, while opioids are necessary for “liking”.
These two substances interact in a comprehensive model of the experiences of reward and pain known as the Motivation-Decision Model. According to this paradigm, actions are accompanied by an unconscious decision-making process that is based primarily on 1) the homeostatic needs of an organism, 2) threats in the environment, and 3) the availability of rewards. In the Motivation-Decision Model, the importance of survival is weighed against possible pain, and a decision is made on whether to pursue a stimulus. Opioids are involved not only in the experience of the reward, but also in inhibiting pain to allow the achievement of a reward if it is considered valuable enough.
Thus, dopamine at the same time draws attention to a reward and cues opioid release to allow for the procurement of it. Attainment of the reward also results in opioid activity as a substrate of pleasure. It seems these two neurotransmitter systems have a complex interaction that may underlie our experience of pleasure, our motivation to obtain it, and also the ability to withstand some pain in order to achieve it.
Dopamine may even have a role in helping us to remember aversive stimuli, although this is still up for debate. Striatal dopamine neurons have been found to be inhibited below baseline levels during exposure to aversive stimuli. It is unclear, however, whether dopamine's role in pain processing involves perception of pain or pain-avoidance learning.
Opioid and dopaminergic systems are closely related anatomically, but exactly which regions mediate the pain and pleasure responses is not yet completely understood. The overall system seems to include the nucleus accumbens (NAc), pallidum, and amygdala. All three areas have been shown to be active in reward and/or pain processing.
Although the history of dopamine is not yet complete, its role has grown substantially from a humble precursor to norepinephrine to one of the major neurotransmitters involved in the experiences of pain and pleasure, experiences that we find inseparable from our understanding of life. A deeper comprehension of this system will have great implications for areas like addiction. It also may prove beneficial in treating disorders like depression or chronic pain, where an ongoing affliction results in a diminished ability to experience pleasure. And, it will probably reveal dopamine’s part in the activity of the brain to be an extremely diverse one, a far cry from a neurotransmitter precursor, or even the “pleasure transmitter”, of the brain.
Leknes, S., Tracey, I. (2008). A common neurobiology for pain and pleasure. Nature Reviews Neuroscience, 9(4), 314-320. DOI:10.1038/nrn2333