Why binge drinking can lead to alcoholism found

A malfunctioning enzyme may be the reason why binge drinking increases the odds of alcoholism, a new study suggests.
Scientists at the Stanford University School of Medicine identified a previously unsuspected job performed by the enzyme, ALDH1a1, in mice.
Jun Ding, assistant professor of neurosurgery and his colleagues showed that blocking ALDH1a1 activity caused mice's consumption of and preference for alcohol to rise to levels equivalent to those observed in mice that had experienced several rounds of the equivalent of binge drinking.
Restoring ALDH1a1 levels reversed this effect.
A key finding in the new study is that in certain nerve cells strongly implicated in addictive behaviours, ALDH1a1 is an essential piece of a previously unknown biochemical assembly line for the manufacture of an important neurotransmitter called GABA.

GABA is the brain's main inhibitory neurotransmitter. It was previously thought that GABA was made in mammalian brains only via a different biochemical assembly line that doesn't involve ALDH1a1.

While GABA is produced widely throughout the brain, the novel GABA-production assembly line identified by Ding's group was observed only in a group of nerve cells known to play a powerful role in addiction.
The new finding has potentially great clinical significance because a drug that could increase GABA synthesis through this alternative assembly line - by boosting ALDH1a1 levels in the brain - could potentially restore the balance in neural circuitry that's been thrown out of kilter by excessive alcohol consumption without dangerously elevating GABA levels elsewhere in the brain.

In the study, researchers wanted to find out whether GABA in dopamine-producing cells might have something to do with addiction.
Ding did a literature search to see how biological systems manufacture GABA. He learned that in plants, GABA can be produced via a biochemical assembly line quite separate from the common, previously known one our brains use.
He found that one step in this alternative GABA-manufacturing pathway is performed by a family of enzymes, aldehyde dehydrogenases, that are better known for being involved in the breakdown of alcohol.
Ding's team verified that the specific family member at work in those dopamine-producing cells was ALDH1a1.

Using advanced laboratory methods to impair ALDH1a1 activity in mice, the scientists saw GABA levels in dopamine-producing nerve cells drop, just as they did when mice with normal ALDH1a1 activity underwent repeated bouts of high alcohol intake - the equivalent of binge drinking.
In behavioural tests, the ALDH1a1-deficient mice showed the same increased alcohol preference and intake as did otherwise normal "binge-drinker" mice. These effects were reversed by manipulations that raised ALDH1a1 levels in the mice.