Translational Psychiatry,
Год журнала:
2025,
Номер
15(1)
Опубликована: Апрель 8, 2025
Dependence
is
a
hallmark
of
alcohol
use
disorder
characterized
by
excessive
intake
and
withdrawal
symptoms.
The
central
nucleus
the
amygdala
(CeA)
key
brain
structure
underlying
synaptic
behavioral
consequences
ethanol
dependence.
While
accumulating
evidence
suggests
that
astrocytes
regulate
transmission
behavior,
there
limited
understanding
role
play
in
present
study
used
combination
viral
labeling,
super
resolution
confocal
microscopy,
3D
image
analysis,
slice
electrophysiology
to
determine
effects
chronic
intermittent
(CIE)
exposure
on
astrocyte
plasticity
CeA.
During
from
CIE
exposure,
we
observed
increased
GABA
transmission,
an
upregulation
astrocytic
GAT3
levels,
proximity
processes
near
CeA
synapses.
Furthermore,
levels
were
positively
associated
with
voluntary
drinking
dependent
rats.
Slice
confirmed
was
functional,
as
unmasked
GAT3-sensitive
tonic
current
A
causal
for
dependence
assessed
using
viral-mediated
overexpression
knockdown
approaches.
However,
or
had
no
effect
somatic
symptoms,
dependence-escalated
intake,
aversion-resistant
drinking,
post-dependent
male
female
Moreover,
intra-CeA
pharmacological
inhibition
did
not
alter
drinking.
Together,
these
findings
indicate
induces
GABAergic
dysregulation
changes
do
appear
be
necessary
related
phenotypes
Human Molecular Genetics,
Год журнала:
2020,
Номер
29(7), С. 1144 - 1153
Опубликована: Март 3, 2020
Abstract
Alcoholism
remains
a
prevalent
health
concern
throughout
the
world.
Previous
studies
have
identified
transcriptomic
patterns
in
brain
associated
with
alcohol
dependence
both
humans
and
animal
models.
But
none
of
these
systematically
investigated
expression
within
unique
cell
types
present
brain.
We
utilized
single
nucleus
RNA
sequencing
(snRNA-seq)
to
examine
transcriptomes
over
16
000
nuclei
isolated
from
prefrontal
cortex
alcoholic
control
individuals.
Each
was
assigned
one
seven
major
by
unsupervised
clustering.
Cell
type
enrichment
varied
greatly
among
neuroinflammatory-related
genes,
which
are
known
play
roles
neurodegeneration.
Differential
analysis
type-specific
genes
altered
alcoholics.
The
largest
number
differentially
expressed
(DEGs),
including
protein-coding
non-coding,
were
detected
astrocytes,
oligodendrocytes
microglia.
To
our
knowledge,
this
is
first
transcriptome
alcohol-associated
gene
any
species
such
for
addictive
substance.
These
findings
advance
understanding
changes
alcohol-dependent
Translational Psychiatry,
Год журнала:
2019,
Номер
9(1)
Опубликована: Окт. 8, 2019
Excessive
alcohol
use
is
the
cause
of
an
ongoing
public
health
crisis,
and
accounts
for
~5%
global
disease
burden.
A
minority
people
with
recreational
develop
addiction
(hereafter
equated
"alcohol
dependence"
or
simply
"alcoholism"),
a
condition
characterized
by
systematically
biased
choice
preference
at
expense
healthy
rewards,
continued
despite
adverse
consequences
("compulsivity").
Alcoholism
arguably
most
pressing
area
unmet
medical
needs
in
psychiatry,
only
small
fraction
patients
receiving
effective,
evidence-based
treatments.
Medications
currently
approved
treatment
alcoholism
have
effect
sizes,
their
clinical
uptake
negligible.
No
mechanistically
new
medications
been
since
2004,
promising
preclinical
results
failed
to
translate
into
novel
This
has
contributed
reemerging
debate
whether
what
extent
represents
condition,
reflects
maladaptive
choices
without
underlying
brain
pathology.
Here,
we
review
this
landscape,
discuss
challenges,
lessons
learned,
opportunities
retool
drug
development
important
therapeutic
area.
Cold Spring Harbor Perspectives in Medicine,
Год журнала:
2020,
Номер
11(2), С. a039339 - a039339
Опубликована: Янв. 27, 2020
Marisa
Roberto,
Dean
Kirson
and
Sophia
Khom
Departments
of
Molecular
Medicine
Neuroscience,
The
Scripps
Research
Institute,
La
Jolla,
California
92037,
USA
Correspondence:
mroberto{at}scripps.edu
Alcohol
intake
remains
controlled
in
a
majority
of
users
but
becomes
"compulsive,"
i.e.,
continues
despite
adverse
consequences,
minority
who
develop
alcohol
addiction.
Here,
using
footshock-punished
self-administration
procedure,
we
screened
large
population
outbred
rats
to
identify
those
showing
compulsivity
operationalized
as
punishment-resistant
self-administration.
Using
unsupervised
clustering,
found
that
this
behavior
emerged
stable
trait
subpopulation
and
was
associated
with
activity
brain
network
included
central
nucleus
the
amygdala
(CeA).
Activity
PKCδ
