Dopamine Drives Feedforward Inhibition to Orexin Feeding System, Mediating Weight Loss Induced by Morphine Addiction
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 21, 2025
Abstract
Feeding
behavior
changes
induced
by
opioid
addiction
significantly
contribute
to
the
worsening
crisis.
Activation
of
reward
system
has
shown
provoke
binge
eating
disorder
in
individuals
with
use
disorder,
whereas
prolonged
exposure
leads
weight
loss.
Understanding
mechanisms
underlying
these
phenomena
is
essential
for
addressing
this
pressing
societal
issue.
This
study
demonstrates
that
loss
resulting
from
feeding
during
morphine
requires
activation
ventral
tegmental
area
dopamine
(DA)
system,
which
suppresses
orexin
center.
Specifically,
DA
exerts
an
inhibitory
effect
on
neurons
lateral
hypothalamus
(LHA)
through
a
feedforward
inhibition
mediated
GABA
LHA,
involving
D1
receptors
(D1R)
and
T‐type
Ca
2+
channels.
Moreover,
addiction‐induced
reduction
body
food
intake
can
be
reversed
D1R
antagonist
SCH23390
chemogenetic
silencing
LHA.
These
findings
delineate
neuromodulatory
mechanism
addiction‐associated
Язык: Английский
Abundance of dopamine and its receptors in the brain and adipose tissue following diet-induced obesity or caloric restriction
Translational research,
Год журнала:
2025,
Номер
280, С. 41 - 54
Опубликована: Май 8, 2025
While
obesity
and
type
2
diabetes
(T2D)
are
associated
with
altered
dopaminergic
activity
in
the
central
nervous
system
adipose
tissue
(AT),
directions
underlying
mechanisms
remain
inconclusive.
Therefore,
we
characterized
changes
abundance
of
dopamine,
its
metabolites,
receptors
DRD1
DRD2
brain
AT
upon
dietary
intervention
or
obesity.
Male
Wistar
rats
were
fed
either
a
standard
pellet
diet,
cafeteria
diet
inducing
insulin
resistance,
calorie-restricted
for
12
weeks.
Abundance
dopamine
examined
regions
relevant
feeding
behavior
energy
homeostasis.
Furthermore,
protein
levels
analyzed
rat
inguinal
epidydimal
human
subcutaneous
omental
from
individuals
without
Rats
diet-induced
displayed
higher
levels,
as
well
receptor
caudate
putamen
nucleus
accumbens
core.
Surprisingly,
caloric
restriction
induced
similar
DRD2,
but
not
brain.
Both
diets
reduced
AT,
upregulated
AT.
obesity,
elevated
only
while
was
both
These
findings
highlight
responses
to
balance,
occurring
We
propose
that
pathways
involved
crosstalk
during
development
T2D.
Язык: Английский
Innervation density governs crosstalk of GPCR-based norepinephrine and dopamine sensors
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 23, 2024
Summary
GPCR-based
fluorescent
sensors
are
widely
used
to
correlate
neuromodulatory
signaling
with
brain
function.
While
experiments
in
transfected
cells
often
reveal
selectivity
for
individual
neurotransmitters,
sensor
specificity
the
frequently
remains
uncertain.
Pursuing
slices
and
vivo,
we
find
that
norepinephrine
dopamine
cross-activate
respective
sensors.
Non-specific
activation
occurred
when
innervation
of
cross-reacting
transmitter
was
high,
silencing
specific
indispensable
interpreting
fluorescence.
Язык: Английский