Binge-drinking during adolescence may perturb brain development and leave lasting effects on genes and behaviour that persist into adulthood, scientists, including one of Indian-origin, have found.
"This may be the mechanism through which adolescent binge-drinking increases the risk for psychiatric disorders, including alcoholism, in adulthood," said lead author Subhash Pandey, professor of psychiatry and director of neuroscience alcoholism research at University of Illinois at Chicago College of Medicine.
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 behaviours and preference for alcohol in adulthood," he said.
The behavioural effects, he said, were due to epigenetic changes - which previous research has shown can be influenced through environmental substances, including alcohol.
To model adolescent binge-drinking in humans, the researchers gave 28-day-old rats alcohol for two days in a row, followed by two days off, and repeated this pattern for 13 days. Some rats were followed into adulthood and observed for abnormal behaviours.
They were offered both alcohol and water, and their alcohol-drinking behaviour was monitored.
Rats exposed to alcohol during adolescence exhibited changes in behaviour that lasted into adulthood, long after exposure to alcohol ended. They showed increased anxiety-like behaviours and drank more alcohol in adulthood.
When the researchers analysed tissue from a part of the brain called the amygdala, they found in the exposed rats that the DNA and histones appeared to be tightly wrapped.
They also found increased levels of a protein called HDAC2, which modifies histones in a way that causes DNA to be wound tighter around them.
These epigenetic changes in turn were linked to lowered expression of a gene that nerve cells need in order to form new synaptic connections.
The researchers observed diminished nerve connectivity in the amygdalae of these affected adult rats.
Intermittent alcohol exposure degrades the ability of the brain to form the connections it needs to during adolescence, researchers found.
"The brain doesn't develop as it should, and there are lasting behavioural changes associated with this," Pandey said.
Researchers also found that when adult rats that had been exposed to alcohol during adolescence were given a cancer drug known to block the activity of HDAC2, the drug restored expression of the gene needed for synapse formation.
The DNA was observed to be less tightly coiled and rats exhibited less anxiety and reduced alcohol intake.
