A population of neurons in the brain that influences whether one drink leads to two has been pinpointed by Texas A&M researchers. The finding could someday lead to a cure for alcoholism and other addictions.
The study, published in the Journal of Neuroscience by scientists at the Texas A&M Health Science Center College of Medicine, finds that alcohol consumption alters the structure and function of neurons in the dorsomedial striatum, a part of the brain known to be important in goal-driven behaviors. The work could be an big step toward creation of a drug to fight alcoholism.
Lead author Jun Wang, M.D., Ph.D., assistant professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M College of Medicine, said:
“Alcoholism is a very common disease. but the mechanism is not understood very well.”
Go Pathway Neurons
Wang and his team have helped us come a little closer to that understanding. Using an animal model, the researchers determined that alcohol actually changes the physical structure of medium spiny neurons, the main type of cell in the striatum.
These neurons can be thought of like a tree, with many branches, and many small protrusions, or spines, coming off of them. They each have one of two types of dopamine receptors, D1 or D2, and so can be thought of as either D1 or D2 neurons.
D1 neurons are informally called part of a “go” pathway in the brain, while D2 neurons are in the “no-go” pathway. In other words, when D2 neurons are activated, they discourage action—telling you to wait, to stop, to do nothing.
It is already known that the neurotransmitter dopamine is involved in addiction, but this study goes further, showing that the dopamine D1 receptor also plays an important role in addiction.
The team found that periodic consumption of large amounts of alcohol acts on D1 neurons, making them much more excitable, which means that they activate with less stimulation.
“If these neurons are excited, you will want to drink alcohol,” Wang said. “You’ll have a craving.”
In other words, when neurons with D1 receptors are activated, they compel you to perform an action—reaching for another bottle of tequila, in this case. This then creates a cycle, where drinking causes easier activation, and activation causes more drinking.
“When you drink alcohol, long-term memory is enhanced, in a way,” Wang said. “But this memory process is not useful—in fact, it underlies addiction since it affects the ‘go’ neurons.”
Because there was no difference in the number of each type of spine in the D2 (no-go) neurons of alcohol-consuming and control models, the researchers realized there was a specific relationship between D1 neurons and alcohol consumption.
“We’re now able to study the brain at the neuron-specific and even spine-specific level,” Wang said.
How do you determine which neuron, which type of neurons or which group of neurons is responsible for a specific disease? That’s what the next part of the study tried to answer.
The alcohol-consuming animal models with the increased mature spines in D1 neurons also showed an increased preference to drink large quantities of alcohol when given the choice.
“Even though they’re small, D1 receptors are essential for alcohol consumption,” Wang said.
Most importantly, when those same animal models were given a drug to at least partially block the D1 receptor, they showed much-reduced desire to drink alcohol. However, a drug that inhibited the D2 dopamine receptors had no effect.
“If we suppress this activity, we’re able to suppress alcohol consumption,” Wang said. “This is the major finding. Perhaps in the future, researchers can use these findings to develop a specific treatment targeting these neurons.”
Jun Wang, Yifeng Cheng, Xuehua Wang, Emily Roltsch Hellard, Tengfei Ma, Hannah Gil, Sami Ben Hamida, and Dorit Ron
Alcohol Elicits Functional and Structural Plasticity Selectively in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum
The Journal of Neuroscience, 19 August 2015, 35(33): 11634-11643; doi: 10.1523/JNEUROSCI.0003-15.2015