Summary: In an innovative study, researchers have designed fruit flies that voluntarily consume cocaine, creating the first fly model for cocaine addiction. In general, flies avoid the medication due to their bitter taste, but by disabled their bitter detection receptors, scientists encouraged addictive behavior within 16 hours of exposure.
This model is an important step to quickly test genetic and neurological mechanisms behind cocaine use disorder. Because flies share many genes related to humans, this research could greatly accelerate the discovery of effective treatments.
Key facts:
Fly addiction model: the genetically altered fruit flies will now self -administer cocaine, imitating addictive behavior. Level receptor block: disable bitter taste receptors allowed flies to prefer cocaine sugar water.
Source: Utah University
For the first time, researchers have created genetically modified fruit flies that can become addicted to cocaine. The flies will self -administer cocaine if they are given the option.
The new model could be immensely valuable for the development of new therapies to prevent and treat cocaine use disorder, a growing and mortal concern that affects approximately 1.5 million people throughout the country.
Inheritance strongly affects the risk of developing cocaine consumption disorder, but the large number of genes involved in the risk of addiction has hindered the determination of what could be the best objectives for therapy.
With their new model of cocaine use disorder, researchers hope to reveal the biology of addiction and find better therapies much faster than was previously possible.
The new results are published in Journal of Neuroscience.
High flight aspirations
Flies and humans react to cocaine in a remarkably similar way, says Adrian Rothenfluh, PHD, associate professor of psychiatry at the University of Utah and the main author of the study. “At low doses, they start running, just like people,” says Rothenflu.
“At very high doses, they are incapacitated, which is also true in people.”
Flies and humans have a lot in common when it comes to addiction. Flies have about 75% of human genes that are known to be involved in the disease, and insects have been fundamental to discovering underlying biology behind other substances dependencies.
Because fruits flies grow rapidly and are easy to perform with genetic experiments, a cocaine use disorder model would be a valuable early step to develop therapies.
There is only one problem, a very significant difference between flies and humans, Rothenfluh says: “Flies do not like cocaine a little.”
His research team found that when he was given an option between sugar water and sugar water with cocaine, the fruit flies constantly chose the free drug option, even when they had been exposed to cocaine previously.
To better understand humans, scientists needed to discover why flies would not take cocaine, and if there were a way to avoid that barrier.
The bitter truth
Travis Philywaw, PHD, first author in the newspaper, suspected that the answer could be in the sense of taste of flies.
“Insects are evolutionarily prepared to avoid vegetable toxins, and cocaine is a vegetable toxin,” says Philyyaw, now scientist to research at the University of Washington, who investigated as a graduate student in the Rothenflu laboratory.
“They have flavor receptors in their ‘arms’, their tarsal segments, so they can put their hand on something before he goes in the mouth and decide: ‘I will not touch that'”.
When observing how the sensory nerves of the flies responded to cocaine, the researchers discovered that the compound strongly activates the bitter sensation taste receptors in the tarsal segments of the flies.
When the researchers silenced the activity of these bitter sensation nerves so that flies could not try bitter flavors, they began to develop a preference for sugar water with cocaine on smooth sugar water.
The dose was important: flies would only voluntarily consume cocaine at low concentrations, but developed a preference markedly, within 16 hours after the first exhibition.
Impact insects
Researchers say this will help them understand human addiction. Now that scientists can study the process in fruit flies, the pipe of new discoveries can accelerate to a large extent, studying hundreds of potentially relevant genes over a much shorter period of time.
“We can climb the investigation so quickly in the flies,” says Philyow.
“We can identify risk genes that could be difficult to discover in more complex organisms, and then we transmit that information to researchers who work with mammalian models. Then, they are able to discover treatment objectives that facilitate the jump of studying animal behavior to the development of human therapeutic.”
Rothenfluh agrees: “We can really begin to understand the mechanisms of cocaine choice, and the more you understand about the mechanism, the more you will have the opportunity to find a therapy that can act on that mechanism.”
In addition to specific therapeutic searches, Rothenfluh says that basic research on the mechanisms of how the human mind, and the mind of the fruit fly can have unexpected impacts.
“Just trying to understand the simple brain of the simple fly can give us ideas that you cannot anticipate,” he emphasizes.
“Basic science is important, and you never know what exciting things you could find that they are shocking to understand the human condition.”
This research is published in Journal of Neuroscience as “bitter detection protects Drosophila from the preference for cocaine consumption dependent on experience.”
Funding: The Work Was Feded by the Huntsman Mental Health Institute, The University of Utah Molecular Medicine Program, and the National Institute of Health, including the National Institute of Diabetes and Digestive and Kidney Designations (Grant Number R01DK110358), The National Institute on Drug Abuse K01DA058919, R21DA049635, AND R21DA040439), and THE NATIONAL INSTITUTE OF ALCOHOL AND ALCOHOLISM ABUSE (GRANT R01AA026818, R01AAA019536-S1 AND R01AA030881). The content is the exclusive responsibility of the authors and does not necessarily represent the official opinions of the National Health Institutes.
On this news of genetic research and addiction
Author: Sophia Friesen
Source: Utah University
Contact: Sophia Friesen – Utah University
Image: The image is accredited to Neuroscience News
Original research: closed access.
“Bitter detection protects Drosophila from the development of the preference for cocaine consumption dependent on the experience” by Adrian Rothenfluh et al. Neuroscience Magazine
Abstract
Bitter detection protects Drosophila from the development of cocaine consumption preferences dependent on the experience
Cocaine is an addictive psychose -stimulant, and the risk of developing cocaine consumption (CUD) disorder is highly inheritable. Little is known about the specific genes and mechanisms that lead to the development of CUD, and currently there are no pharmacotherapies approved by the FDA that can treat it.
Drosophila has demonstrated an effective model organism to identify genes and mechanisms underlying addiction, especially alcohol consumption disorder.
While the flies exposed to the cocaine exhibition characteristics of acute poisoning such as those observed in mammals, including hyperactivity and reduced sleep, to date, there is no preferential self -administration model of cocaine in the flies.
Here, we analyze the consumption of cocaine in Drosophila’s males, as well as the preference in a two options paradigm.
We also investigate mechanisms involved in the detection of cocaine taste using genetic and image tools. We show that cocaine is innate flies and that this avoidance depends on bitter detection.
Full sensory neurons expressing the GR66A bitter receiver are activated after cocaine exposure.
The silencing of these bitter detection neurons or the GR66A mutation reduces the avoidance of cocaine. In a longitudinal choice trial, these flies develop preference for solutions that contain cocaine within 12-18 h, while control flies do not.
Our findings show that bitter sensation protects flies from the development of cocaine self -administer preference.
On the contrary, silencing bitter perception allows us to use Drosophila as a model for the preference for cocaine self -administering experience.
This opens the door to test the human variants associated with CUD for their causal role in cocaine self -administering in this highly manageable model organism.
