Researchers have managed to insert designer brain receptors into cocaine-addicted rats, causing them to forget some of the environmental cues that had previously driven them to seek out the drug.
Though many people think of drug addiction as a purely physical disorder that is caused by the chemical properties of certain substances, in reality the condition is much more complex than that, and is mediated by a range of psychological and physiological factors. Environmental and emotional cues, for example, play a major role in many addictions, as people often learn to associate certain places, people or events with taking drugs.
Encountering these cues even after getting clean can produce an intense urge to use again, which partially explains why so many people relapse even after prolonged periods of abstinence.
Avoiding a relapse can be difficult even after long periods of abstinence. Dima Sidelnikov/Shutterstock
Previous research on animals has indicated that the response to these sorts of cues is regulated by a particular brain region called the ventromedial prefrontal cortex (vmPFC). Because of this, a team of scientists decided to try to hijack some of the neurons in this part of the brain in order to see if they could prevent rats from relapsing when exposed to certain cues.
To do so, they first allowed rats to self-administer cocaine by pressing a lever that not only delivered the drug, but also produced a pulse of light and an audible tone. After a while, the rodents began to associate these stimuli with cocaine, as the study authors explain in the Journal of Neuroscience.
The researchers then inserted what are known as designer receptors exclusively activated by designer drugs (DREADDs) into the rats' brains, by injecting the neurons in the vmPFC with DNA that caused them develop certain receptors on their membranes that differed from naturally occurring ones. These receptors can only be activated by a specific drug, which the team could administer to the rats as and when they pleased.
In doing so, they could be sure to only activate the neurons that had been altered with the DREADDs, allowing them to selectively enhance neuronal activity in a very specific brain pathway.
After forcing the rats to undergo a period of cocaine abstinence, the researchers then gave half of them specialized drugs that activated their DREADDs. When exposed once again to the audible and light cues, those that had received these drugs showed less tendency to relapse and seek out cocaine than those that had not been given these drugs.
Later, all mice were given cocaine, which caused all of them to relapse. As a result, the researchers can be certain that activating the neurons of the vmPFC only prevented relapse as a response to external cues, but didn’t affect the rats’ susceptibility to the chemical properties of the drug itself.
"This new approach for treating drug addiction is exactly what is needed because it is targeted to a specific circuit in the brain regulating addiction," said study co-author Peter Kalivas in a statement.
By controlling the activity of a specific group of neurons it may be possible to alter people's reactions to environmental cues. Iokanan VFX Studios/Shutterstock
By using a similar approach in humans, it may one day be possible for recovering drug addicts to simply take a pill in order to activate their DREADDS, which would then prevent their brains from responding to cues that normally drive them to drugs.
Jamie Peters, who worked with Kalivas on the paper, said that “within my lifetime I would expect to see these virus-mediated gene therapies start to be used in the brain, in a neurosurgical setting.”
