Scientists have known that a region
of the brain called the central nucleus of the amygdala (CeA) plays a role in
behaviors related to alcohol use and consumption in general. It’s been less
known which precise populations of brain cells and their projections to other
brain regions mediate these behaviors. Now, UNC School of Medicine scientists
discovered that specific neurons in the CeA contribute to reward-like
behaviors, alcohol consumption in particular.
Published in
the Journal of Neuroscience, this research pinpoints a
specific neural circuit that when altered caused animal models to drink less
alcohol.
“The fact that these neurons promote
reward-like behavior, that extremely low levels of alcohol consumption activate
these cells, and that activation of these neurons drive alcohol drinking in
animals without extensive prior drinking experience suggests that they may be
important for early alcohol use and reward,” said senior author Zoe McElligott,
PhD, assistant professor of psychiatry and pharmacology. “It’s our hope that by
understanding the function of this circuit, we can better predict what happens
in the brains of people who transition from casual alcohol use to subsequent
abuse of alcohol, and the development of alcohol use disorders.”
McElligott, who is also a member of
the UNC Bowles Center for Alcohol Studies, set out to investigate if a
population of neurons that express a specific neuropeptide (neurotensin or NTS)
contributes to reward-like behaviors and alcohol drinking. She was especially
interested in these neurons in the context of inexperienced alcohol use, such
as when a person first begins to drink alcohol. Also, NTS neurons are a subpopulation
of other neurons in this CeA brain region that have been implicated in anxiety
and fear — known as the somatostatin and corticotropin releasing factor
neurons.
Using modern genetic and viral
technologies in male mice, McElligott and colleagues found that selectively
lesioning or ablating the NTS neurons in the CeA, while maintaining other types
of CeA neurons, would cause the animals to drink less alcohol. This
manipulation did not alter anxiety-like behavior. It also did not affect the
consumption of other palatable liquids such as sucrose, saccharin, and bitter
quinine solutions.
“We found that these NTS neurons in
the CeA send a strong projection to the hindbrain, where they inhibit the
parabrachial nucleus, near the brainstem,” McElligott said.
Using optogenetics — a technique
where light activates these neurons — the researchers stimulated the terminal
projections of the CeA-NTS neurons in the parabrachial and found that this
stimulation inhibited the neurons in the parabrachial. When the scientists
stimulated this projection with a laser in one half of the animal’s box,
animals would spend more time where the stimulation would occur.
Animals also learned to perform a
task to get the laser stimulation to turn on, and they would do this repeatedly,
suggesting that they found this stimulation to be rewarding.
“Furthermore, when we stimulated
this projection, animals would drink more alcohol as compared to when they had
an opportunity to drink alcohol without laser stimulation,” McElligott said. “In
contrast to our study where we ablated the NTS neurons, laser stimulation of
this parabrachial pathway also caused the animals to consume caloric and
non-caloric sweetened beverages. When the animals were presented with regular
food and a sweet food, however, laser stimulation did not enhance the
consumption regardless of the mouse’s hunger state. This suggests that
different circuits may regulate the consumption of rewarding fluids and
solids.”
McElligott and her graduate student
María Luisa Torruella Suarez, the first author of this study, hope to explore
how alcohol experience may change these neurons over time.
“Would these cells respond
differently after animals have been drinking high quantities of alcohol over
time?” McElligott said. “We also want to discover which populations of neurons
in the parabrachial are receiving inputs from these neurons. Fully
understanding this circuit could be the key to developing therapeutics to help
people with alcohol use disorders.”
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