Positron Emission Tomography (PET) scanners, like CT and MRI scanners, produce cross-section images of the human body. PET scanners are the stuff of science fiction in that they employ the same process that powers the warp-drive of the Star Ship Enterprise (matter/anti-matter anihilation). They are commonly used in the study of dopamine mediated function, and can produce images in concert with a radioactive dopamine Antagonist such as Carbon-11 Raclopride. Raclopride is commonly used in medical practice as an antipsychotic. It can, however, be adapted for the PET scanning process by replacing the naturally occurring carbon atoms within the Raclopride molecule with those created in a cyclotron. These atoms have a mass number of 11 and are mildly radioactive. Carbon-11 has a half-life of 20 minutes, and when each atom decays to boron-11 it releases a positron (the anti-matter equivalent of an electron). After release (usually within five millimetres of the source) the positron will interact with an electron. At this point matter/anti-matter annihilation takes place releasing two gamma rays that travel in opposite directions.
The detector of the PET scanner forms a ring around the patient’s body. If a gamma ray passes through the detector it creates a flash of light. The detector senses this flash and takes note of the time it occurred. If two flashes happen at approximately the same time, and on opposite sides of the detector, the software assumes that these are the result of a single Carbon-11 decay. From the precise locations of the two flashes it can deduce where in the body this decay occurred, and from that it can infer that a molecule of Raclopride was at that location. The amount of radiation measured at a particular locale indicates how many Raclopride molecules have bound with dopamine receptors at that point in space. These receptors were unoccupied prior to the arrival of the Raclopride molecule. Raclopride is not able to bind with a receptor that already has a dopamine molecule attached, so if a lower number of Raclopride molecules are detected this indicates that a higher number of dopamine receptors are currently bound with dopamine, or one of its agonists.
Let’s use an analogy here. Imagine you have a black piece of construction paper with ten spots of glue on it. The glue spots represent the dopamine receptors. The glue is clear so the black colour from the paper shows through. This is what the limbic system looks like to the PET scanner prior to introducing the Raclopride into the blood stream; it’s all dark. Now use a fan to blow hundreds of white feathers over the surface of the construction paper. This represents the arrival of the Raclopride molecules as they are carried past in the blood stream. If a feather meets a glue spot it will stick. After that no other feathers can stick to that location because that glue spot is occupied. We could now determine how many glue spots there were by counting the number of white feathers on the card. This is the equivalent of the dopamine receptor density.
A more realistic example would take into account that some of the dopamine receptors are already bound to dopamine molecules, or a dopamine agonist drug, prior to our experiment. To reflect this, we’ll make a new card with another ten glue spots and stick black feathers to half of the glue spots on the card. The next time we blow the white feathers over the card they will only stick to at most five spots. Knowing that each card contained ten glue spots and by comparing the first card with the second card we can calculate how many dopamine receptors were already bound at the start of the experiment.
The PET image below illustrates how cocaine addiction and obesity are related in terms of dopamine receptor occupancy. The normal image exhibits high density Raclopride occupancy, signified here by the reds and yellows, showing that a large number of dopamine receptors were available for binding at the time of the test. In both other cases dopamine receptor availability is greatly reduced. This situation calls for a much larger stimulus to produce a normal response (or signal gain) and will affect the subject’s ability to experience satiation. This naturally drives sensation seeking behaviour and over-consumption. In light of the Rolling Stones’ drug-fuelled lifestyle in the 1960’s this may well be the state of mind described in the song “I can’t get no satisfaction”.
Other drugs have the opposite effect in that they produce an over-satiated state. This factor is desirable when employing stimulant drugs as appetite suppressors, but is a serious impediment to the long-term use of Serotonin based antidepressants which tend to extinguish an active libedo.
We can also use Alcohol and other drugs to illustrate the compounding effect of mixing external and internal dopamine stimuli. One of the most powerfully rewarding dopamine responses is that of aesthetic appreciation. Colour, form, art, music and the wonders of nature all stimulate a pleasure response. When I was first prescribed Ritalin for ADD I visited a friend’s house where a song was playing on the radio. Half way through listening to the song, and enjoying it immensely, I had a realization – “I hate this song, so why am I enjoying it now?” The Ritalin up-regulated dopamine function causing the small amount of dopamine released into the synapses by the song to create a pleasing buzz.
Alcohol can enhance our perception of beauty in the same way. While the following graphic is a joke, and some might consider it to be in poor taste, it does illustrate the principle rather well.
Turning back to the subjective experience of limbic stimulation we find that dopamine does not work alone. Other signalling chemicals also bind with receptors in the nucleus accumbens and affect its firing patterns. Two drugs that follow this course of action (both of which are created naturally within the body) are Oxytocin and beta-endorphin (an analogue of Morphine). Oxytocin modulates dopamine function directly, and Morphine influences dopamine signalling through its action on interneurons. On the subjective level the Oxytocin experience is very similar to that of a dopamine inducer, a response that is exhibited in both sexes. It’s responsible (in conjunction with the Opioids) for the bliss of a warm hug and the coziness of a cuddle with the one you love. Oxytocin also engenders feelings of trust (as revealed by research conducted on Poker playing) and pair bonding (as studied in the lives of monogamous Prairie Voles).
What research reveals is that Oxytocin, Morphine and by extension dopamine, express most aspects of relationship. We are hard-wired for relationship with others. Whether we find someone physically attractive or love them as a friend or family member, dopamine is at the root of each. While the sense of smell is a vitally important component of attraction in animals, human allure relies primarily on vision. The sight of a beautiful face or figure is guaranteed to bring with it a dopamine (attraction) response. It’s also often accompanied by verbal superlatives with religious connotations such as “she was a vision in that dress”, “what an angel” or “she looked simply divine”. Here we begin to see the intersection of dopamine response with spiritual experience.