Source: University of North Carolina Health
Care
Summary: New research pinpoints a specific
neural circuit that when altered caused animal models to drink less alcohol.
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 MarÃa
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."
The National Institutes of Health, The North
Carolina Translational Clinical Science (NC TraCS) Institute, the Alcohol
Beverage Medical Research Foundation, and The UNC Bowles Center for Alcohol
Studies funded this research.
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