A new study published by researchers from Seattle Children’s Research Institute reveals how neurons in the brain fuel drug-seeking behavior following compulsive drug use. Their findings, published online in Addiction Biology, suggest inhibiting one group of neurons’ activity may prove to be a highly effective treatment for reducing relapse in recovering addicts.
While the science of addiction is beginning to show how pathological drug use causes the brain’s “go” pathway to become overactive, little is known about what renders some individuals vulnerable to developing addiction and what protects others against it. There are also few effective treatments available to people who develop a drug addiction, or the approximately 90% of individuals who relapse following addiction treatment.
Dr. Susan Ferguson, a principal investigator in the Center for Integrative Brain Research at Seattle Children’s and senior author on the study, describes how her team used an experimental approach called chemogenetic inhibition to probe the relationship between brain activity and behavior in drug addiction.
Chemogenetics provides insight into neuron-driven behaviors
“Chemogenetics uses a harmless virus to introduce a new gene that causes neurons to express a protein receptor on their surface,” Ferguson said. “When activated, this receptor manipulates the neuron’s activity – either by turning its function up or down. Here, we applied chemogenetics to “turn down” the “go” signal produced by the brain during ongoing cocaine use and studied the effect it had on behavior.”
According to Ferguson, advances using this approach could lead to new therapies to help people overcome addiction. It could also uncover more information about how the brain is involved in addiction, and why some children are especially vulnerable to developing addiction.
For this study, her lab implemented a sophisticated animal model that closely mimics drug use and the development of addiction in humans.
“We wanted to not only simulate actual patterns of drug use in the real world, but also compare recreational drug users, those not likely to develop addictive behaviors, to compulsive drug users most at risk for developing addiction,” Ferguson said.
Drug-Seeking Behavior Reduced in Lab Models
To study the impact of chemogenetic inhibition on drug-seeking behavior in both populations of drug users, researchers provided intermittent access to cocaine in their animal model.
Surprisingly, inhibiting the neurons had no effect on ongoing drug use. Rather, researchers observed a change in drug-seeking behavior following abstinence from drug use. Specifically, subjects previously identified as high-risk for addiction, had less response to cocaine-related cues. Importantly, response to normal, everyday cues remained intact.
Ferguson said the results demonstrate how neuron inhibition using chemogenetics may offer an effective strategy to prevent relapse in recovering drug addicts.
“Effective treatments for pathological drug use need to eliminate undesired addictive impulses when a recovering drug addict encounters cues – say for example, seeing their dealer on the street after rehab – without disrupting their ability to interact with the world around them,” she said. “This balance is critical in the development of new treatments for addiction.”
Ferguson and colleagues plan to apply their findings from this study to a model of heroin addiction to offer new insight into potential treatments for the opioid epidemic sweeping the nation.