IL-18 Signaling in the Rat Central Amygdala Is Disrupted in a Comorbid Model of Post-Traumatic Stress and Alcohol Use Disorder
Cells,
Год журнала:
2023,
Номер
12(15), С. 1943 - 1943
Опубликована: Июль 27, 2023
Alcohol
use
disorder
(AUD)
and
anxiety
disorders
are
frequently
comorbid
share
dysregulated
neuroimmune-related
pathways.
Here,
we
used
our
established
rat
model
of
post-traumatic
stress
(PTSD)/AUD
to
characterize
the
interleukin
18
(IL-18)
system
in
central
amygdala
(CeA).
Male
female
rats
underwent
novel
(NOV)
familiar
(FAM)
shock
stress,
or
no
(unstressed
controls;
CTL)
followed
by
voluntary
alcohol
drinking
PTSD-related
behaviors,
then
all
received
renewed
access
prior
experiments.
In
situ
hybridization
revealed
that
number
CeA
positive
cells
for
Il18
mRNA
increased,
while
Il18bp
decreased
both
male
FAM
stressed
versus
CTL.
No
changes
were
observed
Il18r1
expression
across
groups.
Ex
vivo
electrophysiology
showed
IL-18
reduced
GABAA-mediated
miniature
inhibitory
postsynaptic
currents
(mIPSCs)
frequencies
CTL,
suggesting
GABA
release,
regardless
sex.
Notably,
this
presynaptic
effect
was
lost
NOV
males,
it
persisted
females.
mIPSC
amplitude
CTL
rats,
effects.
Overall,
results
suggest
with
impacts
IL-18-system
and,
sex-related
fashion,
IL-18's
modulatory
function
at
synapses.
Язык: Английский
Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses
Опубликована: Июнь 16, 2022
Alcohol
use
disorder
(AUD)
is
a
chronically
relapsing
disease
characterized
by
loss
of
control
in
seeking
and
consuming
alcohol
(ethanol)
driven
recruitment
brain
stress
systems.
However,
AUD
differs
among
the
sexes:
men
are
more
likely
to
develop
AUD,
but
women
progress
from
casual
binge
drinking
heavy
quickly.
The
central
amygdala
(CeA)
hub
anxiety,
with
corticotropin
releasing
factor
(CRF)-CRF1
receptor
GABAergic
signaling
dysregulation
occurring
dependent
male
rodents.
we
recently
showed
that
synapses
female
rats
less
sensitive
acute
effects
ethanol.
Here,
used
patch
clamp
electrophysiology
examine
dependence
on
CRF-modulation
rat
CeA
transmission
both
sexes.
We
found
naïve
were
unresponsive
CRF
application
compared
males,
although
induced
similar
responsivity
In
situ
hybridization
revealed
females
had
neurons
containing
mRNA
for
CRF1
(Crhr1)
than
dependence,
percentage
Crhr1-expressing
increased,
unlike
males.
Overall,
our
data
provide
evidence
sexually
dimorphic
system
dependence.
Язык: Английский
Moderate prenatal alcohol exposure alters GABAergic transmission and the action of acute alcohol in the CeM of adolescent rats
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 19, 2024
Abstract
Individuals
with
prenatal
alcohol
exposure
(PAE)
are
at
a
higher
risk
for
developing
use
disorder
(AUD).
Using
rat
model
of
PAE
on
gestational
day
12
(G12;
~2
nd
trimesters
in
humans),
critical
period
amygdala
development,
we
have
shown
disruptions
medial
central
(CeM)
function,
an
important
brain
region
associated
the
development
AUD.
In
addition
to
this,
acute
ethanol
(EtOH)
increases
GABA
transmission
CeM
rodents
sex-dependent
manner,
mechanism
that
potentially
contributes
misuse.
How
alters
alcohol’s
effects
within
is
unknown.
Given
these
findings,
investigated
how
may
interact
alter
neuronal
and
synaptic
mechanisms
adolescent
rats
order
understand
PAE-induced
alcohol-related
behaviors.
Under
basal
conditions,
males
showed
reduced
rheobase,
indicative
excitability,
females
reduction
transmission,
indicated
by
lower
spontaneous
inhibitory
postsynaptic
currents
(sIPSCs).
We
found
EtOH
increased
sIPSCs
control
moderate
concentration
(66
mM),
while
only
high
(88
mM).
Adolescent
females,
regardless
status,
were
largely
insensitive
EtOH’s
all
tested
concentrations.
However,
significant
increase
highest
Overall,
findings
support
hypothesis
leads
sex-specific
changes
activity
function.
Future
research
needed
better
specific
which
affects
neurotransmission
individuals
history
PAE.
Язык: Английский