Journal of Neurochemistry,
Journal Year:
2009,
Volume and Issue:
108(6), P. 1323 - 1335
Published: Jan. 12, 2009
Abstract
Drugs
of
abuse
induce
neuroadaptations
through
regulation
gene
expression.
Although
much
attention
has
focused
on
transcription
factor
activities,
new
concepts
have
recently
emerged
the
role
chromatin
remodelling
as
a
prerequisite
for
expression
in
neurons.
Thus,
to
occur,
must
be
decondensed,
dynamic
process
that
depends
post‐translational
modifications
histones.
We
review
here
these
with
particular
emphasis
histone
H3
phosphorylation
at
promoter
specific
genes,
including
c‐
fos
and
jun
.
trace
signalling
pathways
involved
provide
evidence
mitogen
stress‐activated
protein
kinase‐1
(MSK1)
downstream
from
MAPK/extracellular‐signal
regulated
kinase
(ERK)
cascade.
In
response
cocaine,
MSK1
controls
an
early
phase
striatal
action
may
potentiated
by
concomitant
inhibition
phosphatase
1
nuclear
translocation
dopamine‐
cAMP‐regulated
phosphoprotein
Mr
=
32
000.
is
critically
transcription,
cocaine‐induced
locomotor
sensitization.
ERK
plays
dual
drug
addiction
direct
activation
factors
remodelling.
Journal of Neuroscience,
Journal Year:
2006,
Volume and Issue:
26(22), P. 5881 - 5887
Published: May 31, 2006
Long-lasting
vulnerability
to
drug
cue-induced
relapse
a
drug-taking
habit
is
major
challenge
the
treatment
of
addiction.
Here
we
show
that
blockade
memory
reconsolidation,
through
infusion
Zif268
antisense
oligodeoxynucleotides
into
basolateral
amygdala
shortly
before
reexposure
cocaine-associated
stimulus
but
not
simply
training
context,
severely
impaired
subsequently
cue-maintained
cocaine
seeking
under
second-order
schedule
reinforcement
and
abolished
reinstatement
seeking.
This
reduction
in
after
disrupted
reconsolidation
was
only
seen
several
hundred
pairings
with
self-administered
cocaine,
older,
as
well
recent,
memories
were
also
disrupted.
Reconsolidation
may
thus
provide
potential
therapeutic
strategy
for
prevention
Journal of Neurochemistry,
Journal Year:
2006,
Volume and Issue:
100(1), P. 1 - 11
Published: Aug. 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.
PLoS Computational Biology,
Journal Year:
2008,
Volume and Issue:
4(1), P. e2 - e2
Published: Jan. 2, 2008
Drug
addiction
is
a
serious
worldwide
problem
with
strong
genetic
and
environmental
influences.
Different
technologies
have
revealed
variety
of
genes
pathways
underlying
addiction;
however,
each
individual
technology
can
be
biased
incomplete.
We
integrated
2,343
items
evidence
from
peer-reviewed
publications
between
1976
2006
linking
chromosome
regions
to
by
single-gene
strategies,
microrray,
proteomics,
or
studies.
identified
1,500
human
addiction-related
developed
KARG
(http://karg.cbi.pku.edu.cn),
the
first
molecular
database
for
extensive
annotations
friendly
Web
interface.
then
performed
meta-analysis
396
that
were
supported
two
more
independent
identify
18
statistically
significantly
enriched,
covering
both
upstream
signaling
events
downstream
effects.
Five
enriched
all
four
different
types
addictive
drugs
as
common
which
may
underlie
shared
rewarding
actions,
including
new
ones,
GnRH
pathway
gap
junction.
connected
into
hypothetical
network
addiction.
observed
fast
slow
positive
feedback
loops
interlinked
through
CAMKII,
provide
clues
explain
some
irreversible
features
European Journal of Neuroscience,
Journal Year:
2010,
Volume and Issue:
31(12), P. 2308 - 2319
Published: May 27, 2010
Abstract
Memory
reconsolidation
is
the
process
by
which
memories,
destabilised
at
retrieval,
require
restabilisation
to
persist
in
brain.
It
has
been
demonstrated
that
even
old,
well‐established
memories
following
retrieval;
therefore,
memory
could
potentially
be
exploited
disrupt,
or
erase,
aberrant
underlie
psychiatric
disorders,
thereby
providing
a
novel
therapeutic
target.
Drug
addiction
one
such
disorder;
it
both
chronic
and
relapsing,
prominent
risk
factor
for
relapse
episode
presentation
of
environmental
cues
have
previously
associated
with
drugs
abuse.
This
‘cue‐induced
relapse’
can
accounted
psychological
terms
reinforcing
pavlovian
association
between
cue
drug,
thus
influence
behaviour
through
least
three
psychologically
neurobiologically
dissociable
mechanisms:
conditioned
reinforcement,
approach
motivation.
As
each
these
processes
contribute
resumption
drug‐seeking
abstinence,
important
develop
treatments
reduce
re‐established
via
influences
on
all
processes,
order
minimise
subsequent
relapse.
Investigation
mechanisms
underlying
motivation
indicate
they
depend
upon
different
neurochemical
systems,
including
glutamatergic
adrenergic
systems
within
limbic
corticostriatal
circuitry.
We
also
discuss
here
translation
clinic
this
preclinical
work.
