Nav: Home

Opioid gene variant in adolescents reduces reward, may increase later substance abuse risk

November 05, 2018

SAN DIEGO -- Adolescents with a particular variant of an opioid receptor gene have less response in a part of prefrontal cortex that evaluates rewards, compared to those with the other version of the gene, say researchers at Georgetown University Medical Center (GUMC).

For the study, presented Monday at Neuroscience 2018, the annual meeting of the Society for Neuroscience (abstract #7517), the investigators scanned adolescents who have never used drugs or alcohol with functional magnetic resonance imaging (fMRI) while they played a simplified "gambling" game. In some participants, researchers found a muted reward response when the participants were shown when they won, versus lost, a small amount of money.

These results suggest that adolescents with a particular variant of an opioid receptor may be more vulnerable to substance abuse in later years, says the study's senior investigator, John VanMeter, PhD, director of the Center for Functional and Molecular Imaging at GUMC, and an associate professor of neurology.

A possible reason this gene may confer risk is that the diminished response to rewards may compel an individual to over indulge to achieve the same level of pleasure others without the gene variant do, VanMeter says. "Combined with the fact the prefrontal cortex is still developing in adolescence, this may lead to an increased risk for future substance use problems."

The gene in question is the G variant (or allele) of opioid receptor mu (OPRM1). In the brain mu-opioid receptors respond to both internal (e.g., endorphins - such as "runner's high") and external opioids (e.g., morphine and oxycontin used for pain management). The reason the researchers chose to investigate this gene is because a number of studies have linked it to substance abuse. For example, it is more commonly found in adult heroin addicts, and adolescents who have an alcohol use disorder were more than three times likely to have the G-variant, say the researchers.

Adolescents are believed to be at increased risk of misusing drugs because of the differing rates at which parts of their brains develop. By adolescence, the brain's reward area, the striatum and other parts of the limbic system, is fully developed, but the frontal cortex, an area involved in decision making -- evaluating whether the reward is worth the risk -- is not fully matured until early adulthood. This difference means the evaluation of risks versus rewards performed by the frontal cortex is not fully engaged in adolescence.

"The fact that the prefrontal cortex is not fully developed means this is a developmental window and, as such, the use of drugs and alcohol during this period may unalterably inhibit the development of this key part of the brain," says VanMeter.

"Genes are thought to contribute to susceptibility of substance abuse disorders, along with other factors such as family history, poverty, and use among friends," says lead author Veronica C. Mucciarone, a research assistant in VanMeter's lab. "The benefit of this study is that our results suggest that OPRM1 genotype influences the way the brain processes reward before exposure to drugs and alcohol, which is important because this allows us to examine how the gene affects their brains prior to being altered by substance use."

Researchers explored the effects of the G variation in early adolescence, before the participants began using substances. They scanned 115 adolescents, ages 11-13, using fMRI while they played a research-based computerized gambling game. In the game, participants made either risky choices (low odds of winning) or safe choices (high odds of winning), after which they were shown whether they won or lost money.

The study also analyzed self-reported family history of alcohol use/abuse, and while that parental survey found no significant difference between carriers of the OPRM1 G allele, and other alleles, a significant number of participants who carried the G allele reported that they believed their parents drank more alcohol than did the other group of participants.

"Taken together, results showing a heightened awareness of parental alcohol consumption and decreased brain response to reward suggest G-allele carriers may be at increased risk for substance use disorders," says Mucciarone.

VanMeter added, "This indicates that these adolescents have an altered reward system that we should pay attention to, and design prevention strategies to help these children."
-end-
This work is supported by a grant from the National Institute for Alcohol Abuse and Alcoholism (1R01AA01998301)

Additional authors include research assistant Rachel Schroeder, and Benson W. Stevens, PhD, of Georgetown and Diana Fishbein, PhD, of The Pennsylvania State University.

About Georgetown University Medical Center

Georgetown University Medical Center (GUMC) is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter) and Instagram (@gumedcenter).

Georgetown University Medical Center

Related Alcohol Articles:

Sobering new data on drinking and driving: 15% of US alcohol-related motor vehicle fatalities involve alcohol under the legal limit
A new study in the American Journal of Preventive Medicine, published by Elsevier, found that motor vehicle crashes involving drivers with blood alcohol concentrations (BACs) below the legal limit of 0.08 percent accounted for 15% of alcohol-involved crash deaths in the United States.
Alcohol marketing and underage drinking
A new study by a research team including scientists from the Prevention Research Center of the Pacific Institute for Research and Evaluation provides a systematic review of research that examines relationships between exposure to alcohol marketing and alcohol use behaviors among adolescents and young adults.
Alcohol-induced deaths in US
National vital statistics data from 2000 to 2016 were used to examine how rates of alcohol-induced deaths (defined as those deaths due to alcohol consumption that could be avoided if alcohol weren't involved) have changed in the US and to compare the results by demographic groups including sex, race/ethnicity, age, socioeconomic status and geographic location.
Cuts in alcohol duty linked to 2000 more alcohol-related deaths in England
Government cuts to alcohol taxes have had dramatic consequences for public health, including nearly 2000 more alcohol-related deaths in England since 2012, according to new research from the University of Sheffield's School of Health and Related Research (ScHARR).
Integrated stepped alcohol treatment for people in HIV care improves both HIV & alcohol outcomes
Increasing the intensity of treatment for alcohol use disorder (AUD) over time improves alcohol-related outcomes among people with HIV, according to new clinical research supported by the National Institutes of Health.
The Lancet:Targets to reduce harmful alcohol use are likely to be missed as global alcohol intake increases
Increasing rates of alcohol use suggest that the world is not on track to achieve targets against harmful alcohol use, according to a study of 189 countries' alcohol intake between 1990-2017 and estimated intake up to 2030, published in The Lancet.
Alcohol-induced brain damage continues after alcohol is stopped
Now, a joint work of the Institute of Neuroscience CSIC-UMH, in Alicante, and the Central Institute of Mental Health of Mannheim, in Germany, has detected, by means of magnetic resonance, how the damage in the brain continues during the first weeks of abstinence, although the consumption of alcohol ceases.
Does alcohol consumption have an effect on arthritis?
Several previous studies have demonstrated that moderate alcohol consumption is linked with less severe disease and better quality of life in patients with rheumatoid arthritis, but a new Arthritis Care & Research study suggests that this might not be because drinking alcohol is beneficial.
How genes affect tobacco and alcohol use
A new study gives insight into the complexity of genetic and environmental factors that compel some of us to drink and smoke more than others.
Cutting societal alcohol use may prevent alcohol disorders developing -- Otago research reveals
Society must take collective responsibility to reduce the harm caused by alcohol use disorders, a University of Otago academic says.
More Alcohol News and Alcohol Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.