Neuron,
Год журнала:
2023,
Номер
111(23), С. 3789 - 3801.e6
Опубликована: Сен. 29, 2023
Relief,
the
appetitive
state
after
termination
of
aversive
stimuli,
is
evolutionarily
conserved.
Understanding
behavioral
role
this
well-conserved
phenomenon
and
its
underlying
neurobiological
mechanisms
are
open
important
questions.
Here,
we
discover
that
magnitude
relief
from
physical
stress
strongly
correlates
with
individual
resilience
to
depression-like
behaviors
in
chronic
stressed
mice.
Notably,
blocking
causes
vulnerability
behaviors,
whereas
natural
rewards
supplied
shortly
promotes
resilience.
Stress
mediated
by
reward-related
mesolimbic
dopamine
neurons,
which
show
minute-long,
persistent
activation
termination.
Circuitry-wise,
or
inhibition
circuits
downstream
ventral
tegmental
area
during
transient
period
bi-directionally
regulates
depression
These
results
reveal
an
evolutionary
function
identify
neural
substrate
mediating
effect.
Importantly,
our
data
suggest
a
strategy
augmenting
positive
valence
prevent
depression.
Physiological Reviews,
Год журнала:
2020,
Номер
101(2), С. 611 - 681
Опубликована: Сен. 24, 2020
This
article
reviews
the
behavioral
neuroscience
of
extinction,
phenomenon
in
which
a
behavior
that
has
been
acquired
through
Pavlovian
or
instrumental
(operant)
learning
decreases
strength
when
outcome
reinforced
it
is
removed.
Behavioral
research
indicates
neither
nor
operant
extinction
depends
substantially
on
erasure
original
but
instead
new
inhibitory
primarily
expressed
context
learned,
as
exemplified
by
renewal
effect.
Although
nature
inhibition
may
differ
and
either
case
decline
responding
depend
both
generalization
decrement
correction
prediction
error.
At
neural
level,
requires
tripartite
circuit
involving
amygdala,
prefrontal
cortex,
hippocampus.
Synaptic
plasticity
amygdala
essential
for
learning,
cortical
neurons
encoding
fear
memories
involved
retrieval.
Hippocampal-prefrontal
circuits
mediate
relapse
phenomena,
including
renewal.
Instrumental
involves
distinct
ensembles
corticostriatal,
striatopallidal,
striatohypothalamic
well
their
thalamic
returns
(extinction)
excitatory
(renewal
other
phenomena)
control
over
responding.
The
field
made
significant
progress
recent
decades,
although
fully
integrated
biobehavioral
understanding
still
awaits.
Pharmacology & Therapeutics,
Год журнала:
2019,
Номер
204, С. 107402 - 107402
Опубликована: Авг. 27, 2019
Current
medication
for
anxiety
disorders
is
suboptimal
in
terms
of
efficiency
and
tolerability,
highlighting
the
need
improved
drug
treatments.
In
this
review
an
overview
drugs
being
studied
different
phases
clinical
trials
their
potential
treatment
fear-,
anxiety-
trauma-related
presented.
One
strategy
followed
development
refining
improving
compounds
interacting
with
existing
anxiolytic
targets,
such
as
serotonergic
prototypical
GABAergic
benzodiazepines.
A
more
innovative
approach
involves
search
novel
mechanisms
action
using
growing
knowledge
base
concerning
relevant
neurocircuitries
neurobiological
underlying
pathological
fear
anxiety.
The
target
systems
evaluated
include
glutamate,
endocannabinoid
neuropeptide
systems,
well
ion
channels
targets
derived
from
phytochemicals.
Examples
promising
candidates
currently
generalised
disorder,
social
panic
obsessive
compulsive
disorder
or
post-traumatic
stress
ketamine,
riluzole,
xenon
one
common
pharmacological
modulation
glutamatergic
neurotransmission,
neurosteroid
aloradine.
Finally,
D-cycloserine,
MDMA,
L-DOPA
cannabinoids
have
shown
efficacy
enhancing
fear-extinction
learning
humans.
They
are
thus
investigated
augmentative
speeding
up
long-term
effectiveness
exposure-based
psychotherapy,
which
could
render
chronic
dispensable
many
patients.
These
efforts
indicative
a
rekindled
interest
renewed
optimism
discovery
field,
after
decades
relative
stagnation.
