Exploring Cortical Interneurons in Substance Use Disorder: From Mechanisms to Therapeutic Perspectives
The Neuroscientist,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 8, 2025
Interneurons
(INs)
play
a
crucial
role
in
the
regulation
of
neural
activity
within
medial
prefrontal
cortex
(mPFC),
brain
region
critically
involved
executive
functions
and
behavioral
control.
In
recent
preclinical
studies,
dysregulation
INs
mPFC
has
been
implicated
pathophysiology
substance
use
disorder,
characterized
by
vulnerability
to
chronic
drug
use.
Here,
we
explore
diversity
their
connectivity
roles
addiction.
We
also
discuss
how
these
change
over
time
with
exposure.
Finally,
focus
on
noninvasive
stimulation
as
therapeutic
approach
for
targeting
highlighting
its
potential
restore
circuits.
Language: Английский
Advancing Gene Discovery for Substance Use Disorders Using Additional Traits Related to Behavioral Disinhibition
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 30, 2024
Abstract
Importance
Substance
use
disorders
(SUDs)
frequently
co-occur
with
each
other
and
traits
related
to
behavioral
disinhibition,
a
spectrum
of
outcomes
referred
as
externalizing.
Nevertheless,
genome-wide
association
studies
(GWAS)
typically
study
individual
SUDs
separately.
This
single-disorder
approach
ignores
genetic
covariance
between
may
contribute
the
relatively
limited
discoveries
date.
Objective
To
identify
most
effective
model
for
capturing
relationships
externalizing
phenotypes,
optimizing
detection
influences
on
while
maintaining
specificity.
Design
We
used
Genomic
SEM
estimate
SNP
effects
broad
factor
representing
liability
SUDs,
factors
disinhibition
separately,
residualized
SUDs.
Subsequent
gene-based,
tissue
expression,
polygenic
score
(PGS)
analyses
were
compare
ability
these
alternative
approaches
Setting
was
carried
out
from
May
2023
-
September
2024.
Participants
GWAS
summary
statistics
based
samples
European
ancestry
previous
SUD
phenotypes
in
main
multivariate
(
N
>
2.2
million).
two
independent
associations,
family-based
sample
enriched
substance
problems
(COGA;
=
7,530)
population-based
representative
United
States,
(All
Us;
77,442).
Exposures
N/A
Main
Outcomes
Measures
Across
three
(Externalizing;
SUDs;
Behavioral
Disinhibition)
four
(alcohol,
tobacco,
opioid,
cannabis),
we
compared
number,
putative
function,
associations
significant
genomic
risk
loci
genes,
variance
explained
by
scores
outcomes.
Results
identified
genes
uniquely
associated
Externalizing
that
are
relevant
neurobiology
use.
Genes
residual
involved
substance-specific
processes
(e.g.,
metabolism).
The
PGS
accounted
relative
appeared
capture
specific
signals.
Conclusions
Relevance
Our
findings
suggest
modeling
both
behaviors
liabilities
enhances
explains
more
Key
Points
Question
Can
advance
gene
discovery
incorporating
information
about
correlated
disinhibition?
Findings
Combining
common
million
individuals
708
set
Meaning
dysregulation
influenced
variants;
their
joint
contributions
improves
power
prediction.
Language: Английский
An Intricated pas de deux of Addicted Brain and Body Is Orchestrated by Stress and Neuroplasticity
Biochemistry (Moscow),
Journal Year:
2024,
Volume and Issue:
89(11), P. 1863 - 1867
Published: Nov. 1, 2024
Abstract
Dependence
on
psychoactive
substances
is
a
phenomenon
that
based
the
alterations
of
common
molecular
and
cellular
mechanisms,
structures
neuronal
networks
underlying
normal
brain
functioning
realizing
stress
response,
reinforcement
aversion,
learning
memory.
As
result,
aberrant
neuroplasticity
states
associated
with
somatic
changes
are
formed,
which
determine
pathogenesis
symptoms
dependence
at
same
time
can
be
considered
as
targets
for
development
therapies
such
addictions.
An
integrative
scheme
neuroplastic
participation
in
formation
vicious
circle
substance
use
disorders
holistic
approach
presented.
This
special
issue
journal
focuses
mechanisms
disorders.
Language: Английский