Withdrawal from psychostimulants restructures functional architecture of
brain

Date:
September 27, 2021
Source:
University of California - San Diego
Summary:
Researchers describe how withdrawal from nicotine, methamphetamine
and cocaine alters the functional architecture and patterns in the
brains of mice, compared to control animals, a key to developing
addiction treatments.



FULL STORY ========================================================================== Addictive psychostimulants, from nicotine in cigarettes to illicit
drugs like methamphetamine and cocaine, affect different regions of the
brain. The same is believed true during withdrawal; finding a common
brain pathway has proved elusive.


==========================================================================
In a new paper, publishing September 27, 2021 in the journal eNeuro,
a multi- institution team of researchers describe how withdrawal from
nicotine, methamphetamine and cocaine altered the functional architecture
and patterns in the brains of mice, compared to control animals.

They found that each drug produced a unique pattern of activity
in the brain, but that mouse brains in withdrawal shared similar
features. Perhaps more notably, the researchers said all psychostimulants shared a common link: Reduced modularity.

"All brains are organized into semiautonomous groups of neurons with
specific functions, such as the cortex, amygdala and thalamus. Each
region, however, is connected and interacts with other regions performing similar functions, creating a functional unit called a module," said
senior author Olivier George, PhD, professor in Department of Psychiatry
at University of California San Diego School of Medicine. "Think of it
as many different work stations, one station is in control of your mood, another takes care of your needs, and many other stations takes care of
your goals, memories, motivations, sensation, et cetera. The brain needs
many modules to take care of all of these processes at the same time.

"We found that in withdrawal, there was a dramatic decrease in the
number of modules compared to control mice. It's like the whole brain was dedicated to the effect of the lack of drugs, all of the work stations
doing the same thing." That decreased modularity, the authors said,
resulted in a complete restructuring of the brain networks. Reduced
modularity has been shown in several brain disorders in humans, including traumatic brain injury and dementia. It may also be the common link
between drugs of abuse.

To conduct their studies, the scientists implanted osmotic mini-pumps
in mice that contained either nicotine, cocaine, methamphetamine or
saline. The pumps remained in place for one week, with sufficient dosing
and time to create a state of dependence. After the pumps were removed,
the brains of mice were examined using single-cell whole-brain imaging
at the peak of withdrawal symptoms, about eight to 12 hours post-pump
removal.

"We found that cocaine, methamphetamine and nicotine withdrawal all
produced a major shuffling of brain regions with major increases in
functional connectivity throughout the brain compared to control (saline) mice," said George, "with a decrease in modular structuring of the
brain most strongly with methamphetamine and cocaine, then nicotine."
The brains of methamphetamine and cocaine dependent mice were also
very similar, consistent with their shared pharmacology, targeting the dopaminergic system.

This reduced modularity was associated with a shift of networks being controlled by the higher-level cortex to sub-cortical networks. The
effect, said researchers, has been documented in humans after abstaining
from alcohol dependence and in persons suffering from dementia and
traumatic brain injury.

Reduced modularity is associated with cognitive deficits and inflexible behavior which may explain the obsession and compulsion for the drug in
people with substance use disorder.

George said the commonality of this kind of restructuring during
withdrawal from psychostimulants helps explain why these drugs are so addictive. His team is currently using this approach to test experimental medications that may reverse and normalize brain network modularity.

Co-authors include: Adam Kimbrough, UC San Diego and Purdue University;
Marsida Kallupi, UC San Diego; Lauren C. Smith and Sierra Simpson,
UC San Diego and The Scripps Research Institute; and Andres Collazo,
California Institute of Technology.

========================================================================== Story Source: Materials provided by
University_of_California_-_San_Diego. Original written by Scott La
Fee. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Adam Kimbrough, Marsida Kallupi, Lauren C. Smith, Sierra Simpson,
Andres
Collazo, Olivier George. Characterization of the brain functional
architecture of psychostimulant withdrawal using single-cell
whole brain imaging. eneuro, 2021; ENEURO.0208-19.2021 DOI:
10.1523/ENEURO.0208- 19.2021 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210927143649.htm

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