Turning Off Alcohol Abuse

Thanos and his group tested the idea by delivering the gene for D2 receptors directly into the brains of rats that had been trained to drink large quantities of alcohol. This “gene therapy” temporarily increased the rats’ levels of D2 receptors and turned heavy drinkers into light drinkers, and rats who initially drank less into near teetotalers.

Image of test animals

Thanos tests laboratory animals’ preference for alcohol and how much they imbibe in cages set up with two bottles: one with regular drinking water and one with a winelike concentration of alcohol.

“When you see a rat that chooses to drink 80 to 90 percent of its daily fluid as alcohol, and then three days later it’s down to 20 percent, that’s a dramatic drop in alcohol intake — a very clear change in behavior,” Thanos said.

This same approach also worked to decrease alcohol consumption/preference in rats with a genetic preference for drinking very high levels of alcohol, and in genetically engineered transgenic mice with varying levels of dopamine D2 receptors.

Receptor blockade

In another study, Thanos’ group tested the idea that blocking the activity of a different kind of dopamine receptor (D3) in rats with a genetic preference for alcohol might reduce the rats’ feelings of pleasure in response to drinking — and therefore decrease the amount they drank. This time they used a drug that binds to the D3 receptor, preventing dopamine from binding.

The highest doses did indeed decrease the amount of alcohol the animals drank, supporting the idea that such a D3-receptor blockade could possibly be used as a treatment.

Most recently, Thanos has tried this receptor-blocking strategy using a drug that binds to and blocks the brain’s cannabinoid receptors, known as CB1. These brain receptors are directly involved in triggering the reinforcing properties of marijuana and were hypothesized to also play a role in stimulating reward pathways in response to alcohol.