Neurobiology of Disease,
Journal Year:
2024,
Volume and Issue:
199, P. 106590 - 106590
Published: July 10, 2024
The
infralimbic
cortex
(IL)
is
part
of
the
medial
prefrontal
(mPFC),
exerting
top-down
control
over
structures
that
are
critically
involved
in
development
alcohol
use
disorder
(AUD).
Activity
IL
tightly
controlled
by
γ-aminobutyric
acid
(GABA)
transmission,
which
susceptible
to
chronic
exposure
and
withdrawal.
This
inhibitory
regulated
various
neuromodulators,
including
5-hydroxytryptamine
(5-HT;
serotonin).
We
used
intermittent
ethanol
vapor
inhalation
exposure,
a
model
AUD,
male
Sprague-Dawley
rats
induce
dependence
(Dep)
followed
protracted
withdrawal
(WD;
2
weeks)
performed
ex
vivo
electrophysiology
using
whole-cell
patch
clamp
study
GABAergic
transmission
layer
V
pyramidal
neurons.
found
WD
increased
frequencies
spontaneous
postsynaptic
currents
(sIPSCs),
whereas
miniature
IPSCs
(mIPSCs;
recorded
presence
tetrodotoxin)
were
unaffected
either
Dep
or
WD.
application
5-HT
(50
μM)
sIPSC
amplitudes
naive
but
reduced
rats.
Additionally,
5-HT2A
receptor
antagonist
M100907
5-HT2C
SB242084
basal
GABA
release
all
groups
similar
extent.
blockage
receptors
restored
impaired
response
5-HT,
then
resembled
responses
Our
findings
expand
our
understanding
synaptic
inhibition
indicating
antagonism
may
restore
Impairment
serotonergic
modulation
contributes
well-established
rat
AUD
patch-clamp
characterize
serotonin
neurons
ethanol-naive,
ethanol-dependent
(Dep),
ethanol-withdrawn
(WD)
following
from
altered
modulation.
Exogenous
enhanced
it
typical
serotonin-mediated
enhancement
inhibition.
AUD.
Molecular Psychiatry,
Journal Year:
2024,
Volume and Issue:
29(9), P. 2611 - 2621
Published: March 21, 2024
Post-traumatic
stress
disorder
(PTSD)
and
alcohol
use
(AUD)
are
often
comorbid.
Few
treatments
exist
to
reduce
comorbid
PTSD/AUD.
Elucidating
the
mechanisms
underlying
their
comorbidity
could
reveal
new
avenues
for
therapy.
Here,
we
employed
a
model
of
PTSD/AUD,
in
which
rats
were
subjected
stressful
shock
familiar
context
followed
by
drinking.
We
then
examined
fear
overgeneralization
irritability
these
rats.
Familiar
elevated
drinking,
increased
overgeneralization,
alcohol-related
aggressive
signs,
peripheral
hormones.
transcripts
stress-
fear-relevant
genes
central
amygdala
(CeA),
locus
that
regulates
stress-mediated
Compared
with
unstressed
rats,
stressed
exhibited
increases
CeA
Crh
Fkbp5
decreases
Bdnf
Il18.
Levels
Nr3c1
mRNA,
encodes
glucocorticoid
receptor,
males
but
decreased
females.
Transcripts
Il18
binding
protein
(Il18bp),
Glp-1r,
associated
calcitonin
gene-related
peptide
signaling
(Calca,
Ramp1,
Crlr-1,
Iapp)
unaltered.
Crh,
not
Crhr1,
mRNA
was
stress;
thus,
tested
whether
inhibiting
neurons
express
corticotropin-releasing
factor
(CRF)
suppress
PTSD/AUD-like
behaviors.
used
Crh-Cre
had
received
Cre-dependent
vector
encoding
hM4D(Gi),
an
inhibitory
Designer
Receptors
Exclusively
Activated
Drugs.
Chemogenetic
inhibition
CRF
reduced
intake
or
irritability-like
Our
findings
suggest
modulates
PTSD/AUD
comorbidity,
neural
activity
is
primarily
reducing
drinking
trauma-related
behaviors
Psychopharmacology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 17, 2025
Abstract
Rationale
Existing
studies
predominantly
focus
on
the
molecular
and
neurobiological
mechanisms
underlying
Ketamine’s
acute
treatment
effects
post-traumatic
stress
disorder
(PTSD).
This
emphasis
has
largely
overlooked
its
sustained
therapeutic
effects,
which
hold
significant
potential
for
development
of
targeted
interventions.
Objectives
systematic
review
examines
pharmacokinetic
pharmacodynamic
ketamine
PTSD,
differentiating
between
immediate
effects.
Method
A
comprehensive
search
across
databases
(Web
Science,
Scopus,
Global
Health,
PubMed)
grey
literature
yielded
317
articles,
where
29
met
inclusion
criteria.
These
included
preclinical
models
clinical
trials,
through
neurotransmitter
regulation,
gene
expression,
synaptic
plasticity,
neural
pathways
(PROSPERO
ID:
CRD42024582874).
Results
We
found
accumulating
evidence
that
ketamine,
involve
changes
in
GABA,
glutamate,
glutamine
levels,
trigger
re-regulation
BDNF,
enhancing
plasticity
via
such
as
TrkB
PSD-95.
Other
influences
also
include
c-Fos,
GSK-3,
HDAC,
HCN1,
modulation
hormones
like
CHR
ACTH,
alongside
immune
responses
(IL-6,
IL-1β,
TNF-α).
Sustained
arise
from
remodulations
prolonged
expression.
mTOR-mediated
BDNF
alterations
GSK-3β,
FkBP5,
GFAP,
ERK
phosphorylation,
epigenetic
modifications
(DNMT3,
MeCP2,
H3K27me3,
mir-132,
mir-206,
HDAC).
Conclusion
promote
long-term
stability
key
brain
regions,
contributing
to
benefits.
Understanding
behind
ketamine’s
is
critical
developing
safe
effective
personalised
treatments,
potentially
leading
more
recovery.
Neurobiology of Stress,
Journal Year:
2023,
Volume and Issue:
26, P. 100562 - 100562
Published: Aug. 3, 2023
Excessive
alcohol
use
disrupts
neuroimmune
signaling
across
various
cell
types,
including
neurons,
microglia,
and
astrocytes.
The
present
review
focuses
on
recent,
albeit
limited,
evidence
of
sex
differences
in
biological
factors
that
mediate
responses
to
underlying
systems
may
influence
drinking
behaviors.
Females
are
more
vulnerable
than
males
the
neurotoxic
negative
consequences
chronic
drinking,
reflected
by
elevations
pro-inflammatory
cytokines
inflammatory
mediators.
Differences
cytokine,
microglial,
astrocytic,
genomic,
transcriptomic
suggest
females
reactive
neuroinflammatory
changes
after
exposure.
growing
body
supports
innate
immune
modulate
synaptic
transmission,
providing
a
mechanistic
framework
examine
sex-differences
neurocircuitry.
Targeting
be
viable
strategy
for
treating
AUD,
but
research
is
needed
understand
sex-specific
mechanisms.
Addiction Biology,
Journal Year:
2025,
Volume and Issue:
30(5)
Published: May 1, 2025
ABSTRACT
Alcohol
use
disorder
(AUD)
is
associated
with
changes
in
endocrine
and
immune
system
function.
This
study
a
secondary
analysis
aimed
at
investigating
circulating
biomarkers
blood
samples
from
three
groups:
(1)
healthy
controls
(HC,
N
=
12),
(2)
AUD—currently
drinking,
nontreatment
seeking
(CD,
9),
(3)
AUD—abstinent,
treatment‐seeking
(AB,
10;
abstinent
for
least
6
weeks).
We
hypothesized
that
both
biomarker
concentrations
would
be
different
AUD
groups
compared
to
controls.
Immune
included
IL‐8,
IL‐18,
CCL2,
TNF‐α,
IL‐1RA,
IL‐6,
IL‐10.
Endocrine
brain‐derived
neurotrophic
factor
(BDNF),
glucagon‐like
peptide
1
(GLP‐1),
ghrelin,
gastric
inhibitory
(GIP),
growth
hormone,
leptin,
insulin.
Biomarker
were
between
the
while
controlling
age
sex,
associations
behavioral
measures
explored.
IL‐8
elevated
AB
CD
HC
(
F
(2,29)
6.33,
p
0.006,
ƞ
2
0.318).
BDNF
lower
(2,30)
4.34,
0.02,
0.266).
GLP‐1
higher
(2,25)
4.22,
0.03,
0.287).
Exploratory
analyses
combined
showed
of
past
severity,
anxiety/depression
positively
correlated
IL‐18
TNF‐α
negatively
BDNF.
These
results
demonstrate
proteins
are
altered
individuals
history
severe
(AB
group)
In
contrast,
no
group
differences
observed
any
seeking,
currently
drinking
people
group.
Our
findings
highlight
importance
accounting
comorbidities,
status,
especially
when
studying
alcohol‐related
biomarkers.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 14, 2023
Abstract
The
central
nucleus
of
the
amygdala
is
known
to
play
key
roles
in
alcohol
use
and
affect.
Neurotensin
neurons
have
been
shown
regulate
drinking
male
mice.
However,
little
about
which
neurotransmitters
released
by
these
cells
drive
consumption
or
whether
female
Here
we
show
that
knockdown
GABA
release
from
neurotensin
using
a
Nts-
cre-dependent
vGAT-shRNA-based
AAV
strategy
reduces
male,
but
not
female,
This
manipulation
did
impact
avoidance
behavior,
except
fasted
novelty-suppressed
feeding
test,
vGAT
shRNA
mice
demonstrated
increased
latency
feed
on
familiar
high-value
food
reward,
an
effect
driven
In
contrast,
showed
heightened
sensitivity
thermal
stimulation.
These
data
role
for
modulating
rewarding
substances
different
motivational
states.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Nov. 12, 2024
Schizophrenia
is
a
disabling
mental
disorder
that
affects
1%
of
people
over
their
lifetime.
The
etiology
and
mechanism
schizophrenia
are
very
complex,
many
genes
involved
in
different
signaling
pathways
the
this
disease.
According
to
recent
studies,
one
important
mechanisms
altered
regulation
immune
system
inflammation
mechanism.
In
present
study,
we
evaluated
peripheral
blood
expression
pattern
four
lncRNAs
three
protein-coding
treatment-
naïve
patients,
medicated
patients
compared
with
sex
age-matched
controls.
medicated-patients,
levels
IFNG,
IL18RAP,
AC007278.2
were
significantly
up-regulated
(P
<
0.05);
level
IFNG-AS1-001
was
down-regulated
healthy
controls
0.05).
However,
IL18R1,
AC007278.3
IFNG-AS1-003
not
between
these
groups.
treatment-naïve
IFNG-AS1-001,
AC007278.2,
On
other
hand,
Based
on
Spearman
correlation
matrix,
there
significant
patients.
We
also
showed
high
sensitivity
specificity
IFNG-AS1-003,
identification
from
current
study
contributes
further
evidence
understanding
role
pathogenesis
schizophrenia.
Future
research
necessary
establish
validity
as
markers
for
condition.
Успехи физиологических наук,
Journal Year:
2024,
Volume and Issue:
55(4), P. 3 - 26
Published: Dec. 8, 2024
Post-traumatic
stress
disorder
is
a
mental
that
closely
associated
with
dysfunction
of
the
hypothalamic-pituitary-adrenal
axis,
and
for
its
development
required
experience
traumatic
event
causes
negative
emotions
memories
persist
quite
long
time.
The
likelihood
post-traumatic
influenced
both
environmental
factors,
genetic
epigenetic
characteristics
body.
In
this
case
modifications
act
as
dynamic
biomarkers
(“nanotags”)
impact
environment
on
genome
(epigenome),
which
can,
under
certain
conditions,
disappear
or
remain
not
only
in
an
individual
directly
exposed
to
psychogenic
trauma,
but
also
transmitted
over
number
generations.
Review
focuses
possible
mechanisms
intergenerational
transgenerational
inheritance
biological
effects
stress-related
disorders.
Addiction Neuroscience,
Journal Year:
2024,
Volume and Issue:
14, P. 100194 - 100194
Published: Dec. 21, 2024
Alcohol
Use
Disorder
(AUD)
is
a
prevalent
and
debilitating
condition
characterized
by
an
inability
to
control
alcohol
consumption
despite
adverse
consequences.
Current
treatments
for
AUD,
including
FDA-approved
medications
such
as
naltrexone
acamprosate,
have
limited
efficacy
compliance,
underscoring
the
need
novel
therapeutic
approaches.
The
central
amygdala
(CeA)
plays
crucial
role
in
development
maintenance
of
particularly
aspects
associated
with
stress
binge
behaviors.
Recent
research
indicates
neuroimmune
signaling
CeA
emerging
key
factor
this
process.
Chronic
disrupts
signaling,
leading
altered
cytokine
expression
activation
glial
cells,
astrocytes
microglia.
These
changes
contribute
dysregulation
neural
circuits
involved
reward
stress,
perpetuating
alcohol-seeking
behavior
relapse.
This
review
delves
into
how
chronic
exposure
affects
CeA,
contributing
pathophysiology
AUD.
By
focusing
on
impact
cell
activation,
aims
elucidate
mechanisms
which
neuroinflammation
influences
alcohol-related
providing
comprehensive
overview
current
state
research,
identifies
potential
targets
Understanding
complex
interplay
between
behaviors
may
pave
way
more
effective
improved
outcomes
individuals
struggling