New research finds that binge-drinking during adolescence can trigger brain changes that influence certain behaviors during adulthood.
Using an animal model, researchers at the University of Illinois at Chicago College of Medicine showed that during adolescence, some parts of the brain are vulnerable to alcohol. This susceptibility may lead to genetic changes that can cause lasting behavioral effects.
Their findings are reported online in the journal Neurobiology of Disease.
“This may be the mechanism through which adolescent binge-drinking increases the risk for psychiatric disorders, including alcoholism, in adulthood,” says lead author Subhash Pandey.
Pandey and his colleagues used experimental rats to investigate the effects of intermittent alcohol exposure during the adolescent stage of development.
On-and-off exposure to alcohol during adolescence altered the activity of genes needed for normal brain maturation, said Pandey. The gene alterations “increased anxiety-like behaviors and preference for alcohol in adulthood,” he said.
The behavioral effects, he said, were due to “epigenetic” changes — “which previous research has shown can be influenced through environmental substances, including alcohol.” Epigenetic changes can be long-lasting or permanent in an individual. Moreover, previous studies have shown that some epigenetic changes can even be heritable.
Epigenetic changes are chemical modifications of the DNA or of the proteins around which DNA is wound, like thread on a spool. Modification of these proteins, called histones, can change how loosely or tightly the DNA is wound.
Genes that lie within DNA that is tightly wrapped around the histones are less active than they are if the DNA is loosely wrapped. The looser the DNA is coiled, the more accessible are the genes to the cellular machinery that “expresses” them.
Epigenetic changes regulate many processes, including brain development and maturation during adolescence. Changes to the histones expose the genes needed to form new synaptic connections, or to prune unneeded neurons.
Researchers modeled adolescent binge-drinking in humans by giving 28-day-old rats alcohol for two days in a row, followed by two days off. They repeated this pattern for 13 days.
Some rats were followed into adulthood and observed for abnormal behaviors. They were offered both alcohol and water, and their alcohol-drinking behavior was monitored.
Researchers discovered rats exposed to alcohol during adolescence exhibited changes in behavior that lasted into adulthood, long after exposure to alcohol ended. They showed increased anxiety-like behaviors and drank more alcohol in adulthood.
Upon analysis of brain tissue from a part of the brain called the amygdala, researchers found epigenetic changes in the exposed rats. These epigenetic changes in turn were linked to lowered expression of a gene that nerve cells need in order to form new synaptic connections.
Pandey believes the lowered activity of this gene may be due to the tighter winding of its DNA. The diminished expression of the gene persisted in adulthood, even if alcohol exposure was stopped weeks before. The researchers observed diminished nerve connectivity in the amygdalae of these affected adult rats.
“Our study provides a mechanism for how binge-drinking during adolescence may lead to lasting [epigenetic] changes … that result in increased anxiety and alcoholism in adults,” Pandey said.
Intermittent alcohol exposure “degrades the ability of the brain to form the connections it needs to during adolescence.” “The brain doesn’t develop as it should, and there are lasting behavioral changes associated with this.”
Researchers also used the opportunity to perform a pharmacological experiment designed to mimic a potential treatment.
A cancer drug — known to block genetic activity — was administered to the adult rats that had been exposed to alcohol during adolescence. This intervention was found to result in positive changes as the DNA was observed to be less tightly coiled, and the rats exhibited less anxiety and reduced alcohol intake.
While the results were positive, additional research is necessary.
“We aren’t sure if the drug needs to be given long term during adulthood in order to completely reverse the harmful effects of adolescent alcohol exposure,” Pandey said. Further experiments with this and other epigenetic drugs are planned.