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Washington, Oct 26 Just a few drinks in an evening may change how memories are formed at the fundamental, molecular level, a study suggests.
One of the many challenges with the fight against addiction and other substance abuse is the risk of relapse, even after progress toward recovery, said researchers from Brown University in the US.
Even pesky fruit flies have a hankering for alcohol, and because of the molecular signals involved in flies' repetition and avoidance memories are much the same as those in humans, they are a good model for study, they said.
The study, published in the journal Neuron, in flies found that alcohol hijacks this memory formation and neurons, forming cravings.
Researchers uncovered the molecular signalling pathways and changes in gene expression involved in making and maintaining reward memories.
"One of the things I do not understand when they're actually producing neurotoxins," said Karla Kaun, an assistant professor at Brown University.
Led by Emily Petruccelli, who is now an assistant professor at Southern Illinois University in the US, the team used genetic tools to selectively turn off key genes while training the flies where to find alcohol.
This enabled them to see what proteins were required for this reward behavior.
One of the proteins responsible for the flies' preference for alcohol is Notch, the researchers found.
Notch is the first "domino" in a signaling pathway involved in embryo development, brain development and adult brain function in humans and other animals.
Molecular signaling pathways are not unlike a cascade of dominos – when the first domino falls (in this case, the biological molecule activates), it triggers more that trigger more and so on.
One of the downstream dominos in the signaling pathway is a dopamine-2-like receptor, which makes neurons that recognize dopamine, the "feel-good" neurotransmitter.
"The dopamine-2-like receptor is known to be involved in encoding or is pleasing or aversive," Petruccelli said. Alcohol hijacks this conserved memory pathway to form cravings.
In the case of the alcohol reward pathway studied, the signaling cascade did not turn the dopamine receptor gene on or off, or increase or decrease the amount of protein made, Kaun said.
Instead, it had a subtler effect – it changed the version of the protein by a single amino acid "letter" in an important area.
"We do not know what the biological consequences of this change are, but one of the important findings of this study is that getting turned on and off, "Kaun said.
"We think these results are highly likely to translate into forms of addiction, but nobody has investigated that," she said.
Kaun is working with John McGeary, assistant professor at Brown, to look at DNA samples from patients with alcohol abuse.
"If this works the same way in humans, it is enough to activate the pathway, but it returns to normal within an hour," Kaun said.
"After three glasses, with an hour break in between, the pathway does not return to normal after 24 hours." We think this is likely to change the gene expression in memory circuits, "said Kaun.
"Just something to keep in mind with a friend or spouse," she said. SAR
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