While most people think of fruit flies as an annoyance, we have a lot of reasons to be profoundly grateful for them. They have long been a crucial organism for scientific study, particularly with genetics. And more than that: Fruit flies share nearly 75% of the genes that cause disease in humans. That, and their short lifespan, make them an extremely useful to scientists who study human diseases, including alcohol addiction and human behavior.
Bryant University assistant professor Kristin Scaplen is a pioneer in this area. Her work involves gaining a deeper understanding of the neural circuits and mechanisms that contribute to alcohol use and addiction. Her model organism, Drosophila Melanogaster, is the humble fruit fly. Scaplen joined All Things Considered host Arun Rath to discuss her research. What follows is a lightly edited transcript.
Arun Rath: So I talked a bit about the usefulness of the fruit fly, and I remember learning about this as a student. But it’s kind of remarkable that fruit flies can be useful in studying such specific human behaviors as alcohol addiction.
Kristin Scaplen: It’s true. I think that many times when I speak with people outside of science, their first question is, “Wait a minute... Fruit flies have brains?” But in fact, they are a really powerful model organism to answer a lot of these complex questions. They do have a brain. They have a rather simple nervous system, but in fact it supports some really complex behaviors, including learning and memory.
But I think where they become really powerful is with the tools that we have available, which allow us to target individual neurons or subsets of neurons, and we can manipulate their activity with something as simple as turning on the lights or raising the temperature. This is really a resolution that we haven’t achieved in other animal models, which makes them a great model organism for asking a lot of these neural circuitry-based questions.
Rath: And before we talk in more detail about this particular research, could you talk about how neural circuits and alcohol-related behaviors work in terms of addiction with the human organism?
Scaplen: So, we know that alcohol addiction is just a complex problem. It’s a major problem in medicine and in society. Every year, we have three million deaths that can be attributed to the harmful use of alcohol, and excessive drinking is one of the leading causes of preventable deaths in the United States.
But despite this problem, we really have very few effective treatments that, one, help an individual overcome addiction, and two, address their prolonged risk of relapse. We think this is because of alcohol’s complex effects on the brain. And we know that, in fact, it changes and targets neurons, and it changes connections within the brain. So, this is the focus of my work: to understand how alcohol changes the brain.
Rath: When you’re studying this with the fruit flies—they have those same kinds of circuits—do you get the fruit flies addicted?
Scaplen: Yes. Addiction is really complex, right? There are lots of behavioral phenotypes that are associated with addiction. But remarkably, flies do showcase a lot of the behaviors that we see in individuals suffering from alcohol use disorder. So, when you present alcohol to fruit flies at low doses, they start to increase their activity. With longer doses, or higher doses, they become uncoordinated, and ultimately they will sedate, just like humans will.
We can show that with flies, when you present different cues—in this context, they’re odor cues with alcohol intoxication—we do this multiple times, and if we ask the fly which odor they prefer, maybe one that was presented by itself or one that was presented with alcohol, we find that 24 hours later, the flies have this enduring preference for the cues that are associated with alcohol.
And these memories are quite striking. They last upwards of seven days, which is the longest that we’ve tested them. They’re willing to endure an electric shock to get to cues that are associated with alcohol. So, it shows the same kind of willingness to withstand aversive consequences to get their alcohol.
We see that, when we expose flies to alcohol, they will increase their drinking to reach intoxicating doses. They build up tolerances, much like you or I would, and if you withhold alcohol from fruit flies and then give it back to them, they will return to those drinking levels.
Rath: It’s absolutely fascinating, and really, I feel like it gives a sense of what people dealing with addiction are facing in terms of what you’re talking about, with having your brain basically rewired.
Scaplen: Exactly. And so, the question is, how is that brain rewired? And, to your point, are the connections similar? You know, you’ll never find a prefrontal cortex or a hippocampus within the fruit fly, but certainly, the connections of neurons, the connections between neurons are remarkably similar.
So, for instance, dopamine is a neurotransmitter that is often implicated in use disorders, and we see very similar roles for dopamine within the fruit fly.
Rath: Are there other areas of behavior or aspects of neurology that are now open for study with fruit flies, beyond addiction?
Scaplen: Yes. Generally, learning and memory is a really fascinating question that the fruit fly can really contribute to. As I mentioned before, the connections between neurons within our brains are remarkably similar. So you can study learning and memory in a lot of different ways, right? You could ask why we lose some memories and why we can't get rid of other memories?
And, of course, one of the ways in which we study this—within the context of alcohol addiction—is because we do think that there’s a pretty strong memory component here. Memories for cues that are associated with alcohol, those kind of underlie a lot of the persistent cravings that individuals deal with on a daily basis. But you can imagine other instances, like post-traumatic stress disorder, other types of memories that are quite enduring.
There’s a lot of really fantastic work out there looking at memory circuits and relating those to humans.
