Welcome back. Last time we were deep within the mammalian midbrain looking at an idea called dopamine tone. We said that that dopamine tone at the Nucleus Accumbens mapped to Dr. Silkworth’s “restless, irritable, and discontented” base state, one of the core phenomena he found in his addicted patients in the 1930s.

Today, we’re going to look more at why someone might have this restless, irritable, and discontented base state, why someone has low dopamine tone at the midbrain in the first place.

To do that, a couple of more warnings: there’s a tiny little bit of math. It’s not big math; it’s third grade math and you don’t have to remember it. And yes, there’ll be more Nucleus Accumbens, Ventral Tegmental Area, Latin names for things—and you don’t have to remember that either.

But to do what we want to do today, we’re going to focus down on that space between the Ventral Tegmental Area and the Nucleus Accumbens and add two things to this model I didn’t talk about last time. When the Ventral Tegmental Area releases dopamine, there has to be some way for the Nucleus Accumbens to see it. That way is called dopamine receptors. These are proteins on the surface of the cell that have the right shape to see the dopamine, connect with it, and send the signal on. Dopamine goes on and off these receptors thousands of times a second, and it’s all those hits together over time that creates dopamine tone. Also, it turns out that we can’t make enough dopamine to do all this in real time. We have to recycle some of what we’ve already used. To do that, the cells of the ventral tegmental area have a reuptake pump, like a vacuum cleaner, that takes back the dopamine after it’s been released.

Now let’s briefly look at the factors that make up dopamine tone, and here’s the math. Dopamine tone is equal to these three factors [dopamine release, dopamine receptors, time]. The first one is dopamine release. Obviously, you can’t have any dopamine tone if you haven’t released any dopamine. So dopamine release is the first factor in this equation. Also, if the dopamine receptors don’t see the dopamine, there’s no signal, no tone. So dopamine receptors is the second factor in this equation. And finally: time. The dopamine has to be available at the receptors for a sufficient amount of time for the signal to develop and be sent. So time is our third factor.

Let’s take each of these and look at why someone might have a problem. But first, let me tell you that each one of these factors is as important as any of the other ones. If you lower any of these factors, you’re going to lower dopamine tone. If you raise any of these factors, you’ll raise dopamine tone.

Now I want to take each one of these factors and show you why it might be off. Let’s take dopamine release. Maybe you don’t make enough dopamine. Or maybe that balloon-like structure called a vesicle that’s filled with dopamine; maybe it doesn’t have enough dopamine in each vesicle. Or maybe you don’t release enough vesicles per second to get a good signal across.

Let’s take the next factor: dopamine receptors. Maybe you don’t have enough. Or maybe you have plenty but they’re not the right shape and they don’t see the dopamine or they don’t fit the dopamine well or send the signal on well.

Or how about time? Well, maybe that vacuum cleaner dopamine reuptake pump? Maybe it runs too fast and your dopamine doesn’t have enough time at the receptor. Or maybe there are fast-acting enzymes in the area that chew up the dopamine before they can get to the receptor.

What’s important to understand is that everything I just mentioned has a genetic cause. Now there are non-genetic causes of low dopamine tone also; but everything I just said is genetic. That means that you can be restless, irritable, and discontented; you can have low dopamine tone at the Nucleus Accumbens; you can have one Dr. Silkworth’s core phenomena of addiction—without having done anything but being born that way.

Now next time, we’re going to start taking a look at Dr. Silkworth’s other phenomenon: compulsive use. And we’ll see if that can be inborn also.

I hope you join me for that. Until then, be well.

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