Once a neurotransmitter is released it will continue to activate receptors until it is scavenged either through active re-uptake or enzymatic degradation. While the brain is a pretty efficient scavenger of neurotransmitters it isn't perfect and neurotransmitters that aren't scavenged continue to randomly activate receptors and diffuse out of the synaptic cleft. A neurotransmitter that is part of an pulse is called phasic while a neurotransmitter that is awaiting degradation is called tonic.

It was surprising to me that these tonic neurotransmitters have an active role in the brain. Their random activation of receptors on the receiving neuron make it more sensitive, putting it on a hair trigger if you will. The random activation of auto-receptors on the sending neuron inhibit further neurotransmitter release. And when these tonic neurotransmitters diffuse out of the synaptic cleft they can sensitize other neurons nearby or even trigger cell death (in the case of glutamate)

The way that I like to think of it is that a phasic neurotransmitter carries an immediate signal while a tonic neurotransmitter carries a longer term record of phasic activity.

MAO and COMT are two important enzymatic pathways for enzymatic degradation. MAO degrades norepinephrine, serotonin and dopamine while COMT degrades norepinephrine and dopamine. COMT operates by attaching a methyl-donor to the neurotransmitter which is donated by SAM-E. With some consumer grade genetic testing I discovered that I had a defect in betaine homocysteine S-methyltransferase (BHMT) which is one pathway to recycle SAM-E. Supplemental TMG, also called betaine, simulated more BHMT activity for me.

My guess is that lower levels of SAM-E had the effect of elevating tonic dopamine and norepinephrine relative to serotonin by plugging one of the drains.

Splitting this into two replies...

In the popular press dopamine was known as the pleasure or reward neurotransmitter because of its associating with drug addition but with new research that view is slowly changing. While drugs like cocaine or meth produce euphoria research has also shown that dopamine is also released in response to unpleasant stimuli like stubbing your toe or the near miss at the roulette table. My view, which is shared by some researchers, is that dopamine is primarily involved with the salience, or whats important, about an object or situation.

For example, walking down the street the sudden appearance of an aggressive dog or stumbling on gold coin would trigger the release of dopamine and norepinephrine. The release signals to the rest of the brain that something important has happened and to pay attention (focus). The release also simulates memory formation and learning and it makes us slightly less empathetic. It also deactivates sensory suppression and makes us more aware of our surroundings and puts puts movements on a hair trigger. All of which probably facilitates survival.

However in my case the compromised ability to break down dopamine and norepinephrine via the COMT pathway left that system always on. While this contributed to some of my strengths only retrospectively do I now recognize that there were downsides. Enhanced memory formation and learning also means never forgetting and intrusive thoughts in vivid detail an awkward social situation a decade ago. Heightened sensory awareness means that you can't filter out somebody tapping in the next cube or unfamiliar clothing. Twitch like reflexes compromise fine motor skills (like handwriting). And while reduced empathy can help slice through the politics to "do the right thing" it is pretty much a downer in every other way.

Looking back there are also some other things that I can now see with more clarity. I believe that the brain uses the relative levels of tonic dopamine versus tonic serotonin to measure the levels of wanting (or desire) versus getting (or consummation) which I think is the brains proxy for social status. My compromised COMT pathways resulted in my perception of always being subordinate in any work or social situation. Other than the obvious it has some other subtle side effects including an exaggerated sense of justice and rapid escalation of a perceived threat. This seriously hampered career advancement for a long time because it ruled out a leadership role to other people.