Annals of the New York Academy of Sciences,
Journal Year:
2011,
Volume and Issue:
1216(1), P. 99 - 113
Published: Jan. 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.
Pharmacological Reviews,
Journal Year:
2011,
Volume and Issue:
63(1), P. 182 - 217
Published: Feb. 8, 2011
G
protein-coupled
dopamine
receptors
(D1,
D2,
D3,
D4,
and
D5)
mediate
all
of
the
physiological
functions
catecholaminergic
neurotransmitter
dopamine,
ranging
from
voluntary
movement
reward
to
hormonal
regulation
hypertension.
Pharmacological
agents
targeting
dopaminergic
neurotransmission
have
been
clinically
used
in
management
several
neurological
psychiatric
disorders,
including
Parkinson9s
disease,
schizophrenia,
bipolar
disorder,
Huntington9s
attention
deficit
hyperactivity
disorder
(ADHD1),
Tourette9s
syndrome.
Numerous
advances
occurred
understanding
general
structural,
biochemical,
functional
properties
that
led
development
multiple
pharmacologically
active
compounds
directly
target
receptors,
such
as
antiparkinson
drugs
antipsychotics.
Recent
progress
complex
biology
receptor-related
signal
transduction
mechanisms
has
revealed
that,
addition
their
primary
action
on
cAMP-mediated
signaling,
can
act
through
diverse
signaling
involve
alternative
protein
coupling
or
protein-independent
via
interactions
with
ion
channels
proteins
are
characteristically
implicated
receptor
desensitization,
β-arrestins.
One
future
directions
managing
dopamine-related
pathologic
conditions
may
a
transition
approaches
affect
function
precise
postreceptor
intracellular
modalities
either
ligand-biased
pharmacology.
In
this
comprehensive
review,
we
discuss
classification,
basic
structural
genetic
organization,
distribution
brain
periphery,
mechanisms.
addition,
abnormalities
expression,
function,
documented
human
disorders
current
pharmacology
emerging
trends
novel
therapeutic
at
and/or
related
events.
Addiction Biology,
Journal Year:
2007,
Volume and Issue:
12(3-4), P. 227 - 462
Published: July 30, 2007
ABSTRACT
Conditioned
place
preference
(CPP)
continues
to
be
one
of
the
most
popular
models
study
motivational
effects
drugs
and
non‐drug
treatments
in
experimental
animals.
This
is
obvious
from
a
steady
year‐to‐year
increase
number
publications
reporting
use
this
model.
Since
compilation
preceding
review
1998,
more
than
1000
new
studies
using
conditioning
have
been
published,
aim
present
provide
an
overview
these
recent
publications.
There
are
trends
developments
that
literature
last
decade.
First,
as
knockout
transgenic
animals
become
available,
increasingly
used
assess
or
rewards
genetically
modified
Second,
there
still
small
but
growing
on
aspects
pain,
field
pre‐clinical
research
has
so
far
received
little
attention,
because
lack
appropriate
animal
models.
Third,
widely
tolerance
sensitization
rewarding
induced
by
pre‐treatment
regimens.
Fourth,
extinction/reinstatement
procedures
becoming
popular.
interesting
approach
thought
model
certain
relapse
addictive
behavior
previously
almost
exclusively
studied
drug
self‐administration
paradigms.
It
now
also
established
provides
additional
technically
easy
important
phenomenon.
The
enormous
covered
prevented
in‐depth
discussion
many
methodological,
pharmacological
neurobiological
aspects;
large
extent,
presentation
data
had
limited
short
condensed
summary
relevant
findings.
Journal of Neuroscience,
Journal Year:
2008,
Volume and Issue:
28(22), P. 5671 - 5685
Published: May 28, 2008
Psychostimulants
and
other
drugs
of
abuse
activate
extracellular
signal-regulated
kinase
(ERK)
in
the
striatum,
through
combined
stimulation
dopamine
D
1
receptors
(D1Rs)
glutamate
NMDA
receptors.
Antipsychotic
similar
signaling
proteins
striatum
by
blocking
2
(D2Rs).
However,
neurons
which
these
pathways
are
activated
psychotropic
not
precisely
identified.
We
used
transgenic
mice,
enhanced
green
fluorescent
protein
(EGFP)
expression
was
driven
D1R
promoter
(
drd1a
-EGFP)
or
D2R
drd2
-EGFP).
confirmed
-EGFP
striatonigral
striatopallidal
neurons.
Drd2
also
expressed
cholinergic
interneurons,
whereas
no
either
detected
GABAergic
interneurons.
Acute
cocaine
treatment
increased
phosphorylation
ERK
its
direct
indirect
nuclear
targets,
mitogen-
stress-activated
kinase-1
(MSK1)
histone
H3,
exclusively
D1R-expressing
output
dorsal
nucleus
accumbens.
Cocaine-induced
c-Fos
Zif268
predominated
but
observed
D2R-expressing
One
week
after
repeated
administration,
cocaine-induced
responses
were
decreased,
with
exception
striatum.
The
remained
confined
to
In
contrast,
acute
haloperidol
injection
ERK,
MSK1,
H3
only
induced
c-fos
zif268
predominantly
Our
results
demonstrate
that
specifically
two
completely
segregated
populations
striatal
neurons,
providing
evidence
for
selective
mechanisms
exert
their
long-term
effects.
British Journal of Pharmacology,
Journal Year:
2014,
Volume and Issue:
172(1), P. 1 - 23
Published: Oct. 17, 2014
The
variety
of
physiological
functions
controlled
by
dopamine
in
the
brain
and
periphery
is
mediated
D1,
D2,
D3,
D4
D5
GPCRs.
Drugs
acting
on
receptors
are
significant
tools
for
management
several
neuropsychiatric
disorders
including
schizophrenia,
bipolar
disorder,
depression
Parkinson's
disease.
Recent
investigations
receptor
signalling
have
shown
that
receptors,
apart
from
their
canonical
action
cAMP-mediated
signalling,
can
regulate
a
myriad
cellular
responses
to
fine-tune
expression
dopamine-associated
behaviours
functions.
Such
mechanisms
may
involve
alternate
G
protein
coupling
or
non-G
involving
ion
channels,
tyrosine
kinases
proteins
such
as
β-arrestins
classically
involved
GPCR
desensitization.
Another
level
complexity
growing
appreciation
roles
played
heteromers.
Applications
new
vivo
techniques
significantly
furthered
understanding
receptors.
Here
we
provide
an
update
current
knowledge
regarding
complex
biology,
physiology
pharmacology
Journal of Neuroscience,
Journal Year:
2007,
Volume and Issue:
27(26), P. 6995 - 7005
Published: June 27, 2007
The
molecular
basis
of
l-3,4-dihydroxyphenylalanine
(l-DOPA)-induced
dyskinesia
(LID),
one
the
major
hindrances
in
current
therapy
for
Parkinson9s
disease,
is
still
unclear.
We
show
that
attenuation
cAMP
signaling
medium
spiny
neurons
striatum,
achieved
by
genetic
inactivation
dopamine
and
cAMP-regulated
phosphoprotein
32
kDa
(DARPP-32),
reduces
LID.
also
that,
dyskinetic
mice,
sensitized
cAMP/cAMP-dependent
protein
kinase/DARPP-32
leads
to
phosphorylation/activation
extracellular
signal-regulated
kinases
1
2
(ERK1/2).
increase
ERK1/2
phosphorylation
associated
with
results
activation
mitogen-
stress-activated
kinase-1
(MSK-1)
histone
H3,
two
downstream
targets
ERK
involved
transcriptional
regulation.
In
line
these
observations,
we
found
c-Fos
expression
abnormally
elevated
striata
mice
affected
Persistent
enhancement
cascade
implicated
generation
Thus,
pharmacological
using
SL327
(α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile),
an
inhibitor
mitogen-activated
kinase/ERK
kinase,
MEK,
during
chronic
l-DOPA
treatment
counteracts
induction
dyskinesia.
Together,
indicate
a
significant
proportion
abnormal
involuntary
movements
developed
response
are
attributable
hyperactivation
striatal
pathway
including
sequential
DARPP-32,
ERK1/2,
MSK-1,
H3.