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Interviewer: How to treat addiction based on what we understand about the neuroscience of addiction. That's next on The Scope.

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Interviewer: Eric Garland is a clinical researcher and practicing licensed psychotherapist at the University of Utah. Neuroscience is looking at a new way of thinking about addiction which then would guide how we would treat addiction. Give me a little background, how the school of thought in neuroscience treats addiction right now or thinks about addiction.

Eric: Sure. So there's really a way of understanding addiction that has emerged out of the past couple of decades, and there's been a lot of research and time and energy put into understanding this problem, and what we're coming to realize is that addiction is really a process of normal learning gone awry. The same processes in the brain that facilitate normal learning get hijacked by drugs of abuse.

Normally when we learn things, when we have an experience and the experience is rewarding, this tells the brain to do this thing again. And so we learn that that activity or that experience is valuable. We get some sort of pleasure or reward out of it.

In everyday life that might be good relationships with people that we care about, doing activities and hobbies that we love. It might be something simple like enjoying the pleasure of a tasty, healthy meal or a beautiful sunset or the snow on the mountains, but as a person becomes addicted, the effects of addictive drugs on the dopamine system in the brain cause changes in this normal learning pattern such that what was once rewarding becomes less rewarding and the brain becomes more and more dependent on drugs to receive the same amount of pleasure and reward.

Even drug use itself in the beginning is highly stimulating and rewarding to the brain. It produces a surge of dopamine release. But over time, the drug itself produces less reward and drug use becomes more and more of an automatic habit. People start to use drugs on automatic pilot without getting any pleasure out of it. It's just like any other habit we have that we do. The more you do it, the easier it becomes, the more automatic it becomes, the less you have to think about it, and that habit starts to become triggered by cues. For example, if you're an alcoholic driving past the bar or driving past a liquor store, or if you're a smoker and you smoke in social situations.

Interviewer: Or just even driving. I've known smokers that I could predict when they pull a cigarette out based on where we were in a trip.

Eric: Exactly.

Interviewer: By the time we hit the stop sign at the end of the street, a cigarette is going to be out. By the time we hit here, another cigarette's going to be out.

Eric: Exactly.

Interviewer: So wow, okay.

Eric: And they may not even intend to be smoking it. They may not even realize that they're smoking it. A lot of smokers have the experience of sort of looking down and seeing that half their cigarette's gone up and they don't even remember smoking it. It just becomes an automatic habit. It doesn't even give them pleasure anymore.

Interviewer: And then worse yet, the other things that didn't give them pleasure, don't give them pleasure anymore.

Eric: That's right.

Interviewer: So what do you do with that point? How do you break this cycle?

Eric: Right, and so the cycle, it gets worse because the things that used to give them pleasure are no longer giving them pleasure and the drug isn't giving them pleasure. The person is in a deficit. They're in a negative mood state and that really drives them to take higher and higher doses of the drug just to feel okay. And there's the addictive cycle right before you.

Interviewer: So how do you solve that?

Eric: Well, if this is the problem then it seems that we need treatments that can do two things. One, they can help a person become aware of the automatic habit of addiction, to become aware of when cues are triggering this automatic habit so that the person can begin to exercise some self-control over the automatic habit.

And then two, we need treatments that can help people to find a way to enjoy pleasure in life again, to teach the brain to relearn how to feel a sense of pleasure and reward from everyday activities that used to bring them pleasure.

Interviewer: And what are some of those things that you can do to start discovering pleasure in life again?

Eric: Yeah, so that is where a technique called mindfulness comes into play because mindfulness is really, although it's based on some ancient techniques for training the mind, we're coming to realize now with neuroscience that this approach actually strengthens both of those processes, both self-control over automatic habits as well as increasing attentional focus that might enhance the experience of reward.

Interviewer: Let me jump back for a second. So this is just one way of looking at addiction, what you've described to me. How sure are we that this is the way it is? I mean, how have they figured out this much?

Eric: There've been multiple millions of dollars invested by the National Institutes of Health, specifically the National Institute on Drug Abuse and the National Institute on Alcoholism devoted to this topic. These studies range from studies with animals, studies with humans and even studies down to the cellular level to understand how neurons communicate to each other and how drugs actually affect neurotransmission.

One simple way that this has been shown to be the case is by putting people in a brain scanner and watching how their brains respond when they're shown drug-related cues on a screen, for example, pictures of cigarettes, and showing activations in brain circuits in the reward center of the brain, and as addiction progresses seeing activations in the dorsal striatum which is the part of the brain that's involved in habit responses, and conversely seeing the opposite effects with regard to naturally rewarding queues.

So if you put somebody in a brain scanner and this person has developed addiction and you show them, for example, cues of smiling babies or beautiful sunsets or couples holding hands, the brain responds less sensitively to those cues.

Interviewer: It seems like some people are more prone to addiction. With this way of thinking, why would that be, or is that a false statement to begin with?

Eric: No, there's quite a bit of research looking into, for example, the genetic factors that predispose somebody to addiction, but in the line of discussion that we're talking about, people vary to the extent to which they're naturally sensitive to rewards. They vary to the extent to which they seek out novelty, they're sensation-seeking is the term, and they also vary to the extent to which they can control their impulses. Some people are just better naturally at stopping themselves and exerting self-control than others.

But my interest as a therapist is how people can train those capacities so that no matter where you start from, you can train your mind to strengthen self-control and strengthen your ability to experience pleasure in everyday life.

Interviewer: Are there any resources that if somebody wanted to learn more on their own that you could steer them towards?

Eric: There are a number of practitioners in the community that are practicing mindfulness-based therapies and there are also a number of providers in the community that are practicing other evidence-based treatments for addiction like motivational interviewing and cognitive behavioral therapy.

Interviewer: How is this way of treating being approached right now by the rest of the addiction community, people that don't subscribe to this philosophy?

Eric: This is a really hot topic right now in the addiction research field in terms of the importance of reward, the importance of sensitivity to natural reward as a predictor of addiction-related problems, but the idea that we could actually improve this capacity in somebody who is addicted and has lost the ability to feel pleasure in everyday life, this is a brand new thing. So it's a pretty hot topic and controversial.

Interviewer: Yeah, and not only overcoming addiction but actually maybe even be happier than they were ever before.

Eric: Exactly. It has a lot of applications to other issues, too, like depression or chronic pain and just improving the healthy response in life.

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Interviewer: Fish that can repair their own brain up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs, the Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Adam Douglass, Assistant Professor of Neurobiology and Anatomy at the University of Utah. Dr. Douglass, you have this cool result where fish basically repair their own brain. Tell me what you saw?

Dr. Douglass: In particular, we're interested in populations of neurons in the fish brain that release dopamine. So its cells that make the neurotransmitter dopamine release it into the brain and in figuring out what those cells do to behavior. Within our department, I collaborate closely with a group led by Rich Dorsky, whose lab is also interested in fish brains, but in different aspects of it, in particular, regenerative aspects of it.

The experiment that we did with Richard's lab was to ablate those neurons initially using a chemical technique that caused all of the cells, give or take a few, to disappear. What we found is that over the course of almost immediately, really, starting within a day or two of the ablation, the cells start to grow back such that by a couple of weeks after the initial insult in which we've destroyed the cell population, we have a number of neurons in the structure making dopamine that's almost identical to the number that we started with.

Interviewer: You also saw that the fish were able to regain their behavior too.

Dr. Douglass: Right. What we found is that immediately following the ablation and coincident with the loss of these dopamine neurons, the fish swim a whole lot less. If you put a group of young zebrafish, baby zebrafish into a dish, they normally swim around out pretty ruddily. They keep moving continuously and in contrast, after the ablation, the fish more or less just laid there. They could still move and, in particular, it was encouraging to see that if you startle the animals by tapping the dish or leaning over it; things that they normally don't like and try to get away from, they still swim around quite a bit. So it wasn't just a gross defect in the animal's ability to move. It seemed to be something related to its motivation to do so that was missing.

Interviewer: The fish have motivation?

Dr. Douglass: Yeah, they normally like to swim.

Interviewer: And that was able to come back over time after you . . .

Dr. Douglass: Yeah, and it came back in a way that more or less directly paralleled the regeneration of the neurons that we had killed. So while we think that there're probably other regenerative events or neurogenesis events that are ongoing in hypothalamus, some of which may have been upregulated following the ablation of these cells, the fact that the behavior comes back in a more or less proportional way relative to the number of these cells that are present makes us think that these probably are the neurons that are responsible for setting these weights, these tendencies to move or not move. And we are able to support that using other experimental techniques.

Interviewer: So you think a specific cell type regenerates and mediates this recovery. What cell type are you looking at and why is it interesting?

Dr. Douglass: The cells that we study make dopamine, this neurotransmitter which most people have heard about in the context of reward and things like addiction. It's certainly interesting in those contexts, but it turns out that dopamine does a lot of different things in human behavior as well as in fish behavior. For instance, as anybody who's learned about Parkinson's disease knows, dopamine neurons have a very important connection to locomotor behaviors, movement behaviors in every system where dopamine neurons exist.

There's also a variety of other stuff, literally dozens of different behavioral functions for this one neural transmitter. And one of the things I find interesting about this is that we have a poor ability to explain exactly how one molecule does so many different things in behavior. The answer at some level is almost certainly in the fact that there are multiple different brain regions that contain different populations of dopamine neurons. What my lab is trying to do is the relatively straightforward task of seeing what happens to behavior when you manipulate activity in these cells.

Interviewer: Do you think other cells in the brain might be able to regenerate this way as well?

Dr. Douglass: Historically, there's been this notion that brains don't grow back. Certainly the human brain . . . that its regenerative capacity that's capacity for new cell growth falls to zero following very early development. What we've come to realize over the past decades is that that's not true. It's a reasonable approximation for how the system works in the sense that neurogenesis does really fall off as you enter into adulthood and, unfortunately, cell death does increase.

But as people have looked more closely, they've realized that there are several brain areas where there's a significant amount of neurogenesis going on all the time through adulthood. That includes the area of the brain that we're studying, the hypothalamus, both in mammals and in fish exhibits lots of new cell growth.

Interviewer: Are there any implications for what this could mean for us?

Dr. Douglass: Our work is really unique in that it demonstrates not only that there's a cell population that comes back but it's a dopaminergic cell population and it's a dopaminergic cell population with a direct function in locomotor behavior. If you look at mammalian systems, unfortunately, the substantia nigra, the brain area containing dopamine neurons that are affected in Parkinson's disease, is not regenerative. That's one of the reasons that cell loss and Parkinson's ultimately leads to massive defects in locomotion and ultimately the inability to move.

Our brain area, the hypothalamus, which contains the dopamine neurons that we're studying is not functionally equivalent to the substantia nigra in a strict sense, but the fact that these neurons in fish are both connected to locomotion and have the ability to regenerate probably hold some clues as to how regeneration might be made to work in the human brain areas that are affected by neurodegenerative disease.

It's not to say that we're on the brink of having some therapeutic insight to this. That's far from the case, but I do think that it's reasonable to think that we'll learn something about how these systems work and potentially what's missing in the case of the substantia nigra dopamine neurons that makes them not able to regenerate. If you can identify those things, then that gives you potential sites for therapeutic and intervention down the line.

Announcer: Interesting, informative and all in the name of better health, this is The Scope Health Sciences Radio.