Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 29, 2024
Binge
drinking
(BD)
contributes
strongly
to
the
harms
of
alcohol
use
disorder.
Most
rodent
models
do
not
result
in
binge-level
blood
concentrations
(BACs),
and
better
understand
individual
sex
differences
neurobiological
mechanisms
related
BD,
outbred
rat
strains
would
be
valuable.
Here,
we
developed
a
novel
BD
model
where
after
3+
months
intermittent
access
20%
Wistar
rats
drank,
twice
week,
with
two
5-minute
intake
(what
called
Two-shot)
separated
by
10-minute
break.
Our
findings
showed
during
Two-Shot
that
most
animals
reached
≥
80mg%
BAC
levels
(when
briefly
food-restricted).
However,
when
increasing
from
30%,
40%,
or
50%,
titrated
similar
levels,
suggesting
rapid
sensing
effects
even
front-loading.
was
reduced
both
sexes
naltrexone
(1mg/kg),
validating
suppression
clinical
therapeutic
agent.
Further,
propranolol
(β
adrenergic
receptor
antagonist)
prazosin
(α1
female
but
male
at
lower
dose.
Thus,
our
results
provide
for
suggest
binging
is
more
sensitive
modulation
than
males,
perhaps
providing
sex-related
therapy.
Neurobiology of Stress,
Год журнала:
2023,
Номер
25, С. 100547 - 100547
Опубликована: Июнь 4, 2023
Impairments
in
the
function
of
hypothalamic-pituitary-adrenal
(HPA)
axis
and
enhanced
glucocorticoid
receptor
(GR)
activity
central
amygdala
(CeA)
are
critical
mechanisms
pathogenesis
alcohol
use
disorder
(AUD).
The
GR
antagonist
mifepristone
attenuates
craving
AUD
patients,
consumption
models,
decreases
CeA
γ-aminobutyric
acid
(GABA)
transmission
alcohol-dependent
rats.
Previous
studies
suggest
elevated
male
alcohol-preferring
Marchigian-Sardinian
(msP)
rats,
but
its
contribution
to
heightened
GABA
driving
their
characteristic
post-dependent
phenotype
is
largely
unknown.
We
determined
Nr3c1
(the
gene
encoding
GR)
transcription
female
msP
Wistar
rats
using
situ
hybridization
studied
acute
effects
(10
μM)
interaction
with
ethanol
(44
mM)
on
pharmacologically
isolated
spontaneous
inhibitory
postsynaptic
currents
(sIPSCs)
electrically
evoked
potentials
(eIPSPs)
ex
vivo
slice
electrophysiology.
Female
both
genotypes
expressed
more
GRs
than
males,
suggesting
a
sexually
dimorphic
regulation
activity.
Mifepristone
reduced
sIPSC
frequencies
(GABA
release)
eIPSP
amplitudes
sexes,
not
counterparts;
however,
it
did
prevent
ethanol-induced
increase
In
regulates
GABAergic
signaling
under
basal
conditions,
indicative
intrinsically
active
GR.
Thus,
represents
key
mechanism
contributing
maladaptive
behaviors
associated
AUD.
Abstract
Frontloading
is
an
alcohol
drinking
pattern
where
intake
skewed
towards
the
onset
of
access.
This
study
aimed
to
identify
brain
regions
involved
in
frontloading.
Whole
imaging
was
performed
63
C57Bl/6J
(32
female,
31
male)
mice
that
underwent
8
days
binge
using
drinking‐in‐the‐dark
(DID).
On
Days
1–7
received
20%
(v/v)
or
water
for
2
h.
Intake
measured
1‐min
bins
volumetric
sippers.
Day
were
perfused
80
min
into
DID
session
and
brains
extracted.
Brains
processed
stain
Fos
protein
iDISCO+.
Following
light
sheet
imaging,
ClearMap2.1
used
register
Allen
Brain
Atlas
detect
Fos+
cells.
For
network
analyses,
patterns
characterize
as
frontloaders
non‐frontloaders
a
change‐point
analysis.
Functional
correlation
matrices
calculated
each
group
from
log
10
values.
Euclidean
distances
these
R
values
clustering
determine
modules
(highly
connected
groups
regions).
In
males,
access
decreased
modularity
(three
both
non‐frontloaders)
compared
(seven
modules).
females,
opposite
effect
observed.
Alcohol
(nine
frontloaders)
increased
(five
Further,
different
served
hubs
control
groups.
conclusion,
consumption
led
fewer,
but
more
densely
connected,
males
not
females
we
several
brain‐wide
signatures
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
24(1), С. 388 - 388
Опубликована: Дек. 26, 2022
Post-traumatic
stress
disorder
(PTSD)
and
alcohol
use
(AUD)
are
prevalent
neuropsychiatric
disorders
frequently
co-occur
concomitantly.
Individuals
suffering
from
this
dual
diagnosis
often
exhibit
increased
symptom
severity
poorer
treatment
outcomes
than
those
with
only
one
of
these
diseases.
Lacking
standard
preclinical
models
limited
the
exploration
neurobiological
mechanisms
underlying
PTSD
AUD
comorbidity.
In
review,
we
summarize
well-accepted
model
paradigms
criteria
for
developing
successful
We
also
outline
how
affect
each
other
bidirectionally
in
nervous
nuclei
have
been
heatedly
discussed
recently.
hope
to
provide
potential
recommendations
future
research.
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Июнь 18, 2024
Abstract
Binge
drinking
(BD)
contributes
strongly
to
the
harms
of
alcohol
use
disorder.
Most
rodent
models
do
not
result
in
binge-level
blood
concentrations
(BACs),
and
better
understand
individual
sex
differences
neurobiological
mechanisms
related
BD,
outbred
rat
strains
would
be
valuable.
Here,
we
developed
a
novel
BD
model
where
after
3+
months
intermittent
access
20%
Wistar
rats
drank,
twice
week,
with
two
5-min
intake
(what
called
Two-shot)
separated
by
10-min
break.
Our
findings
showed
during
Two-Shot
that
most
animals
reached
≥
80
mg%
BAC
levels
(when
briefly
food-restricted).
However,
when
increasing
from
20
30%,
40%,
or
50%,
titrated
similar
levels,
suggesting
rapid
sensing
effects
even
front-loading.
was
reduced
both
sexes
naltrexone
(1
mg/kg),
validating
suppression
clinical
therapeutic
agent
for
human
problem
drinking.
Further,
propranolol
(β-adrenergic
receptor
antagonist)
prazosin
(α1-adrenergic
female
but
male
at
lower
dose.
Thus,
our
results
provide
suggest
binging
is
more
sensitive
adrenergic
modulation
than
males,
perhaps
providing
sex-related
therapy.
Frontiers in Molecular Neuroscience,
Год журнала:
2022,
Номер
15
Опубликована: Июль 5, 2022
Alcohol
use
disorder
is
a
highly
significant
medical
condition
characterized
by
an
impaired
ability
to
stop
or
control
alcohol
use,
compulsive
seeking
behavior,
and
withdrawal
symptoms
in
the
absence
of
alcohol.
Understanding
how
modulates
neurocircuitry
critical
for
long
term
binge-like
such
as
central
amygdala
(CeA),
may
lead
development
novel
therapeutic
strategies
treat
disorder.
In
clinical
studies,
reduction
volume
has
been
linked
with
susceptibility
relapse
use.
Preclinical
studies
have
shown
involvement
CeA
effects
lesions
showing
drinking,
manipulations
cells
altering
drinking.
A
great
deal
work
that
acute
alcohol,
well
chronic
exposure
via
intake
dependence
models,
alters
glutamatergic
GABAergic
transmission
CeA.
The
CeA,
however,
contains
heterogeneous
cell
populations
distinct
subregional
differences
neurocircuit
architecture
which
influence
mechanism
function
overall.
current
review
aimed
parse
out
on
medial
lateral
subregions
what
role
neuroinflammatory
markers,
endocannabinoid
system,
most
commonly
studied
neuropeptide
systems
play
mediating
these
effects.
better
understanding
type
more
selective
pharmacological
interventions
