Texas A&M team finds
neuron responsible for alcoholism
Newswise,
September 3, 2015 — Scientists have pinpointed a population of neurons in the
brain that influences whether one drink leads to two, which could ultimately
lead to a cure for alcoholism and other addictions.
A
study, published in the Journal
of Neuroscience by researchers 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 findings could be an important
step toward creation of a drug to combat alcoholism.
“Alcoholism
is a very common disease,” said Jun Wang,
M.D., Ph.D., the lead author on the paper and an assistant professor in the
Department of Neuroscience and Experimental Therapeutics at the Texas A&M
College of Medicine, “but the mechanism is not understood very well.”
Now,
Wang and his team have helped 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.
Although
it is well known that the neurotransmitter dopamine is involved in addiction,
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.”
That is to say, 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.
These
changes in activation of D1 neurons might be related to the physical changes
happening at the sub-cellular level in brains that have been exposed to
alcohol. They have longer branching and more of the mature, mushroom-shaped
spines — the type that stores long-term memories — than their abstaining counterparts.
Conversely,
the placebo group, the ones not exposed to alcohol, tended to have more of the
immature versions of the mushroom-shaped spines in D1 neurons of their brains.
The total number of spines didn’t change in the two groups, but the ratio
between mature and immature was dramatically different between the alcohol
group and the placebo group. This has important implications for memory and
learning in drug addiction.
“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.
Furthermore,
and perhaps most excitingly, 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.”
The
study, which was co-authored with researchers from the University of California
San Francisco, was supported by a grant from the National Institute on Alcohol
Abuse and Alcoholism (NIAAA).
“My
ultimate goal is to understand how the addicted brain works,” Wang said, “and
once we do, one day, we’ll be able to suppress the craving for another round of
drinks and ultimately, stop the cycle of alcoholism.”
