The Effects of Nociceptin Receptor Agonist, SR-8993, on Cocaine Addiction Related Behavior.

1. J U L I E T T E P O Z Z U O L I
The Effects of Nociceptin Receptor
Agonist, SR-8993, on Cocaine
Addiction Related Behavior

2. Background
 Cocaine is a triple reuptake inhibitor which means it
inhibits the reuptake of dopamine, serotonin, and
norepinephrine.
This inhibition leads
to a higher
concentration of
dopamine, serotonin,
and norepinephrine
and thus, an
exaggerated euphoric
effect

3. Nociceptin Receptor
 Nociceptin and its receptor (NOP-R) is densely
located along the reward pathways of the brain
 Previous research also shows that NOP agonism
leads to a reduction of cocaine induced dopamine
release in the nucleus accumbens.
 This leads me to believe that a NOP-R agonist may
be able to attenuate the rewarding aspects of cocaine.

4. SR-8993
 SR-8993 is a highly selective NOP agonist.
 The purpose of this study is to determine whether
SR-8993, and thus NOP agonism, effects the
acquisition of cocaine addiction in mice.

5. Materials and Methods
 Conditioned Place Preference Paradigm:
 Rectangular box with two distinct chambers
separated by a wall
The CPP is a three phase test:
1. Pretest
2. Conditioning
3. Posttest

6. Conditioned Place Preference
 Pretest:
 Mice are put into chamber with door open and were allowed
to explore apparatus for 15 mins. Time on each side was
tracked.
 Conditioning:
 Mornings: Mice injected with cocaine and put into one side
(door closed) for 30 minutes
 Afternoons: Mice injected with saline and put into “Most
Preferred” chamber (door closed) for 30 minutes
 This conditions mice to associate one side with drug-induced
euphoria and the other with no pleasure.

7. Conditioned Place Preference (CPP)
 Posttest: Door is opened and mouse is allowed to
roam freely. Time on each side is measured.
 After conditioning, the mouse will spend much more time on
the cocaine-paired side
 Level of addiction is established by calculation a
Preference Score:
 Time in Cocaine paired side Posttest – Pretest
 A Preference Score above 100 means the mouse has
acquired an addiction

8. Inclusion of SR-8993
 SR-8993 is injected 30 minutes prior to cocaine
conditioning to see if it affects the acquisition of the
addiction
 12 mice are injected with SR-8993, 12 mice are
injected with control vehicle.

9. Results
 Preference Score:
Time in coc side
Post – Pre
 SR-8993 fails to
disrupt addiction
related behavior
SR
-8993
Vehicle
0
100
200
300
400
500
CPP Acquisition
Treatment
PreferenceScore

10. Discussion
 SR-8993 did not affect cocaine related behavior in
the acquisition phase of cocaine addiction
 This suggests that selective targeting of the NOP
receptor is not sufficient to weaken the link between
cocaine and reward.

11. Works Cited
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