Pivotal role of orexin signaling in the posterior paraventricular nucleus of the thalamus during the stress-induced reinstatement of oxycodone-seeking behavior
Journal of Psychopharmacology,
Год журнала:
2024,
Номер
38(7), С. 647 - 660
Опубликована: Июнь 18, 2024
The
orexin
(OX)
system
has
received
increasing
interest
as
a
potential
target
for
treating
substance
use
disorder.
OX
transmission
in
the
posterior
paraventricular
nucleus
of
thalamus
(pPVT),
an
area
activated
by
highly
salient
stimuli
that
are
both
reinforcing
and
aversive,
mediates
cue-
stress-induced
reinstatement
reward-seeking
behavior.
Oral
administration
suvorexant
(SUV),
dual
receptor
(OXR)
antagonist
(DORA),
selectively
reduced
conditioned
oxycodone-seeking
behavior
alcohol-seeking
dependent
rats.
Язык: Английский
Orexin-mediated Motivated Arousal and Reward Seeking.
Peptides,
Год журнала:
2024,
Номер
180, С. 171280 - 171280
Опубликована: Авг. 17, 2024
Язык: Английский
The Complexly Parcellated, Yet Quantitatively Reduced, Orexinergic/Hypocretinergic System of Humans
The Journal of Comparative Neurology,
Год журнала:
2025,
Номер
533(2)
Опубликована: Фев. 1, 2025
ABSTRACT
The
phylogenetic
contextualization
of
human
neuroanatomy
is
crucial
for
understanding
the
positive,
neutral,
and/or
negative
effects
therapeutic
interventions
derived
from
animal
models.
Here
we
determined
parcellation
of,
and
quantified,
orexinergic
(or
hypocretinergic)
neurons
in
hypothalami
humans
several
species
primates,
including
strepsirrhines
(two
species),
platyrrhines
cercopithecoids
(three
hominoids
species,
humans).
strepsirrhines,
platyrrhines,
presented
with
three
distinct
clusters
neurons,
revealing
an
organization
like
that
observed
most
mammals.
In
hominoids,
additional
cluster
was
found
tuberal
region
hypothalamus,
termed
optic
tract
extension.
only,
parvocellular
dorsomedial
hypothalamus.
complex
primates
studied.
Total
numbers
nonhuman
were
strongly
correlated
to
brain
mass
(
P
uncorr
=
1.2
×
10
−6
),
every
doubling
leading
∼1.5‐times
increase
neuron
number.
contrast,
have
approximately
74,300
which
significantly
less
than
205,000
predicted
using
primate
regression
a
∼1363
g.
We
conclude
although
system
terms
parcellation,
potential
associated
functional
specializations,
this
quantitatively
paradoxical
having
lower
neuronal
number
expected
∼1363‐g
brain.
Язык: Английский
Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation
British Journal of Pharmacology,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 24, 2024
Abstract
The
orexin
(also
known
as
hypocretin)
system,
consisting
of
neuropeptides
orexin‐A
and
orexin‐B,
was
discovered
over
25
years
ago
immediately
identified
a
central
regulator
sleep
wakefulness.
These
peptides
interact
with
two
G‐protein
coupled
receptors,
1
(OX
)
2
receptors
which
are
capable
coupling
to
all
heterotrimeric
subfamilies,
but
primarily
transduce
increases
in
calcium
signalling.
Orexin
neurons
regulated
by
variety
transmitter
systems
environmental
stimuli
that
signal
reward
availability,
including
food
drug
related
cues.
also
activated
anticipation,
stress,
cues
predicting
motivationally
relevant
information,
those
drugs
abuse,
engage
neuromodulatory
systems,
dopamine
the
ventral
tegmental
area
(VTA)
respond
these
signals.
As
such,
have
been
characterized
motivational
activators
coordinate
range
functions,
feeding
arousal,
allow
individual
critical
for
survival.
This
review
focuses
on
role
orexins
appetitive
motivation
highlights
pathologies
inappropriately
high
levels
motivated
arousal
(overeating,
anxiety
substance
use
disorders)
versus
is
impaired
(depression).
Язык: Английский
Evaluating the efficacy of the selective orexin 1 receptor antagonist nivasorexant in an animal model of binge‐eating disorder
International Journal of Eating Disorders,
Год журнала:
2024,
Номер
57(7), С. 1418 - 1432
Опубликована: Март 8, 2024
Abstract
Objective
Test
the
efficacy
of
selective
orexin
1
receptor
(OX1R)
antagonist
(SO1RA)
nivasorexant
in
an
animal
model
binge‐eating
disorder
(BED)
and
study
its
dose–response
relationship
considering
free
brain
concentrations
calculated
OX1R
occupancy.
Compare
nivasorexant's
profile
to
that
other,
structurally
diverse
SO1RAs.
Gain
understanding
potential
changes
orexin‐A
(OXA)
neuropeptide
deltaFosB
(ΔFosB)
protein
expression
possibly
underlying
development
phenotype
rat
used.
Method
Binge‐like
eating
highly
palatable
food
(HPF)
rats
was
induced
through
priming
by
intermittent,
repeated
periods
dieting
access
HPF,
followed
additional
challenge
with
acute
stress.
Effects
were
compared
SO1RAs
ACT‐335827
IDOR‐1104‐2408.
OXA
neurons
neuronal
fibers
as
well
ΔFosB
OXA‐ΔFosB
co‐expression
studied
relevant
regions
using
immuno‐
or
immunofluorescent
histochemistry.
Results
All
dose‐dependently
reduced
binge‐like
effect
sizes
comparable
positive
control
topiramate,
at
unbound
drug
selectively
blocking
OX1Rs.
Nivasorexant's
maintained
upon
chronic
dosing
under
conditions
involving
more
frequent
stress
exposure.
Priming
for
treatment
resulted
only
minor
few
areas.
Discussion
Selective
blockade
rats.
Neither
nor
proved
be
a
useful
classifier
their
phenotype.
The
current
results
formed
basis
clinical
phase
II
trial
BED,
which
unfortunately
not
efficacious
placebo.
Public
Significance
Nivasorexant
is
new
investigational
(BED).
It
underwent
testing
proof
concept
humans
but
manuscript
investigated
drug's
reducing
behavior
sweet
fat
diet
initially
laid
foundation
trial.
Язык: Английский
Emerging medications and pharmacological treatment approaches for substance use disorders
Pharmacology Biochemistry and Behavior,
Год журнала:
2024,
Номер
248, С. 173952 - 173952
Опубликована: Дек. 22, 2024
Язык: Английский
Sex‐ and age‐dependent impacts of nicotine and ethanol binge drinking on the brain: Insights from preclinical research
Journal of Neurochemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 24, 2024
Abstract
Electronic
cigarette
use
among
adolescents
is
a
growing
concern,
not
only
due
to
the
high
incidence
of
co‐use
with
other
substances,
such
as
alcohol,
but
also
fact
brain
still
maturing
during
this
period.
Combined
exposure
alcohol
and
nicotine
leads
plastic
adaptation
crucial
circuits
in
brain,
which
can
contribute
development
addiction.
It
well
established
that
facilitate
binge
drinking,
vice‐versa,
sex‐,
age‐
exposure‐dependent
manner.
Nonetheless,
central
mechanisms
underlying
synergistic
relationship
between
these
two
substances
emergence
differential
behavioural
traits
dependent
on
factors
remain
underexplored.
Preclinical
studies
continue
provide
valuable
insights
into
mechanisms.
Here,
we
discuss
recent
preclinical
findings
report
changes
characteristic
addiction
following
consumption,
primarily
models
vaping
use;
neural
impacted
by
intake
focus
adolescent
brain.
image
Язык: Английский