Annals of the New York Academy of Sciences,
Год журнала:
2011,
Номер
1216(1), С. 99 - 113
Опубликована: Янв. 1, 2011
Drug‐induced
alterations
in
gene
expression
throughout
the
reward
circuitry
of
brain
are
likely
components
persistence
drug‐addicted
state.
Recent
studies
examining
molecular
mechanisms
controlling
drug‐induced
transcriptional,
behavioral,
and
synaptic
plasticity
have
indicated
a
direct
role
for
chromatin
remodeling
regulation
stability
drug‐mediated
neuronal
programs,
subsequent
promulgation
addictive
behaviors.
In
this
review,
we
discuss
recent
advances
our
understanding
phenomena—or
epigenetics,
by
one
definition—that
contribute
to
drug
addiction,
with
hope
that
such
mechanistic
insights
may
aid
development
novel
therapeutics
future
treatments
addiction.
Journal of Neurochemistry,
Год журнала:
2006,
Номер
100(1), С. 1 - 11
Опубликована: Авг. 29, 2006
Abstract
Glutamate
receptors
regulate
gene
expression
in
neurons
by
activating
intracellular
signaling
cascades
that
phosphorylate
transcription
factors
within
the
nucleus.
The
mitogen‐activated
protein
kinase
(MAPK)
cascade
is
one
of
best
characterized
this
regulatory
process.
Ca
2+
‐permeable
ionotropic
glutamate
receptor,
mainly
NMDA
receptor
subtype,
activates
MAPKs
through
a
biochemical
route
involving
‐sensitive
Ras‐guanine
nucleotide
releasing
factor,
/calmodulin‐dependent
II,
and
phosphoinositide
3‐kinase.
metabotropic
(mGluR),
however,
primarily
‐insensitve
pathway
transactivation
tyrosine
kinases.
adaptor
Homer
also
plays
role
As
an
information
superhighway
between
surface
nucleus,
active
specific
(Elk‐1
CREB),
thereby
distinct
programs
expression.
regulated
contributes
to
development
multiple
forms
synaptic
plasticity
related
long‐lasting
changes
memory
function
addictive
properties
drugs
abuse.
This
review,
focusing
on
new
data
from
recent
years,
discusses
mechanisms
which
different
types
activate
MAPKs,
features
each
MAPK
regulating
expression,
importance
glutamate/MAPK‐dependent
addiction.
Journal of Neuroscience,
Год журнала:
2007,
Номер
27(46), С. 12732 - 12742
Опубликована: Ноя. 14, 2007
The
extracellular
signal-regulated
kinase
(ERK)/MAPK
(mitogen-activated
protein
kinase)
cascade
has
been
established
as
a
potent
regulator
of
gene
transcription
in
long-term
memory
formation,
but
the
precise
mechanisms
this
regulation
are
poorly
understood.
ERK
does
not
directly
affect
many
its
nuclear
targets,
rather
must
act
through
intermediary
kinases.
In
study,
we
investigated
role
mitogen-
and
stress-activated
1
(MSK1),
downstream
ERK,
chromatin
remodeling
during
hippocampus-dependent
formation.
Mice
lacking
MSK1
show
impaired
Pavlovian
fear
conditioning
spatial
learning,
well
deficiency
histone
phosphorylation
acetylation
hippocampus
after
training.
addition,
hippocampal
slices
from
knock-out
mice
exhibit
both
activation
pathway
vitro
.
vivo
injections
deacetylase
inhibitor,
sodium
butyrate,
fail
to
alleviate
deficit
mice.
Finally,
demonstrate
cAMP
response
element-binding
(CREB)
training,
which
persists
butyrate
injection.
This
suggests
that
CREB
represent
parallel
targets
function.
Our
study
identifies
an
important
memory.
Annals of the New York Academy of Sciences,
Год журнала:
2011,
Номер
1216(1), С. 99 - 113
Опубликована: Янв. 1, 2011
Drug‐induced
alterations
in
gene
expression
throughout
the
reward
circuitry
of
brain
are
likely
components
persistence
drug‐addicted
state.
Recent
studies
examining
molecular
mechanisms
controlling
drug‐induced
transcriptional,
behavioral,
and
synaptic
plasticity
have
indicated
a
direct
role
for
chromatin
remodeling
regulation
stability
drug‐mediated
neuronal
programs,
subsequent
promulgation
addictive
behaviors.
In
this
review,
we
discuss
recent
advances
our
understanding
phenomena—or
epigenetics,
by
one
definition—that
contribute
to
drug
addiction,
with
hope
that
such
mechanistic
insights
may
aid
development
novel
therapeutics
future
treatments
addiction.
