Cocaine reinstates extinguished food responding in male cynomolgus monkeys with a history of self-administering cocaine under a concurrent drug vs. food choice paradigm
Journal of Pharmacology and Experimental Therapeutics,
Год журнала:
2025,
Номер
392(3), С. 103387 - 103387
Опубликована: Янв. 15, 2025
The
rate-dependency
principle
postulates
that
"stimulants"
tend
to
increase
low
baseline
rates
of
response
and
decrease
high
responses.
One
exception
this
is
stimulants
do
not
typically
responses
has
been
extinguished.
However,
drug
self-administration
studies
showed
stimulant
pretreatments
reinstated
extinguished
drug-maintained
goal
study
was
determine
the
effects
noncontingent
cocaine
on
food-maintained
responding
in
3
male
cynomolgus
monkeys
with
extensive
experience.
Monkeys
had
a
>4-year
history
self-administering
under
concurrent
versus
food
schedule
reinforcement.
For
study,
only
discriminative
stimulus
(SD)
signaling
fixed-ratio
30
reinforcement
studied,
previous
cocaine-associated
SD
illuminated
(inactive).
In
experiment
1,
effect
(1-5
pellets)
(0.03-0.3
mg/kg
i.v.)
studied.
all
monkeys,
5
pellets
at
least
1
dose
significantly
increased
responding;
were
larger
than
those
food.
2,
behavioral
mechanisms
mediating
these
cocaine-induced
increases
Following
administration
0.3
cocaine,
no
illuminated,
occurred
both
previously
active
(food)
inactive
(cocaine)
manipulanda.
When
given
SDs
more
switch.
These
findings
suggest
can
influence
direct
cocaine.
Increases
nondrug-reinforced
behaviors
could
have
clinical
implications
related
relapse.
SIGNIFICANCE
STATEMENT:
long-term
context
nondrug
alternative,
maintained
by
delivery
pellets,
suggesting
reinstatement
may
be
measuring
relapse
"drug-seeking."
Importantly,
self-administered
brain
behavior
cannot
determined
absence
systematically
studying
ongoing
behavior.
Язык: Английский
Animal models of cocaine use: importance of social context and co-use
Trends in Pharmacological Sciences,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Reinforcing Effects of the Novel Dopamine Transport Inhibitors Jjc8-088 and Jjc8-091 in Monkeys
Опубликована: Янв. 1, 2024
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DOI
Язык: Английский
Contrasting the Reinforcing Effects of the Novel Dopamine Transport Inhibitors JJC8-088 and JJC8-091 in Monkeys: Potential Translation to Medication Assisted Treatment
Journal of Pharmacology and Experimental Therapeutics,
Год журнала:
2024,
Номер
392(1), С. 100033 - 100033
Опубликована: Сен. 20, 2024
Despite
considerable
efforts,
there
remains
no
FDA-approved
medications
for
cocaine
use
disorder
(CUD).
One
strategy
to
mitigate
craving
and
relapse
is
elevate
dopamine
(DA).
The
DA
transport
inhibitor
releaser
d-amphetamine
has
been
shown
decrease
self-administration
(SA),
although
it
abuse
liability.
Recently,
several
modafinil
analogues
reduced
SA
in
rats
monkeys,
including
JJC8-088,
characterized
as
"cocaine
like"
rats,
JJC8-091,
"atypical"
not
by
rats.
present
studies
evaluated
the
reinforcing
effects
of
both
compounds
monkeys
under
conditions.
For
Experiment
1,
four
male
cocaine-experienced
rhesus
self-administered
(0.001-0.3
mg/kg/injection),
JJC8-088
JJC8-091
(0.1-3.0
mg/kg/injection)
a
progressive-ratio
(PR)
schedule
reinforcement.
Both
JJC
functioned
reinforcers
with
equal
strength
cocaine.
Although
was
less
potent
than
cocaine,
had
similar
potencies.
2,
one
two
females
drug-naïve
cynomolgus
responded
on
fixed-ratio
food
at
rates
higher
saline
all
three
monkeys.
In
3,
from
2
concurrent
drug
vs.
choice
paradigm
given
access
or
these
At
doses
one-half
log-units
used
but
chosen
over
food.
Together,
results
demonstrate
that
while
may
be
some
conditions,
its
strength,
presence
an
alternative
reinforcer,
substantially
Significance
Statement
have
efficacy
reducing
nonhuman
primates.
This
study
found
maintained
responding
However,
when
reinforcer
during
session,
reinforcing,
suggesting
viable
candidate
CUD
since,
human
population,
alternatives
are
often
available.
Язык: Английский
Selective dopamine D3 receptor partial agonist (±)VK4-40 reduces the reinforcing strength of d-amphetamine but not cocaine in rhesus monkeys responding under a progressive-ratio schedule of reinforcement
Drug and Alcohol Dependence,
Год журнала:
2024,
Номер
265, С. 112494 - 112494
Опубликована: Ноя. 5, 2024
Язык: Английский