charles drew university of medicine and science 4 th annual drug abuse research symposium
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Endogenous Opioid Regulation of Goal-Directed and Habitual Behavior. Kate M. Wassum , Ingrid C. Cely, Dr. Sean B. Ostlund, Dr. Nigel T. Maidment, Dr. Bernard W. Balleine. Charles Drew University of Medicine and Science 4 th Annual Drug Abuse Research Symposium September 26 th 2008. - PowerPoint PPT PresentationTRANSCRIPT
Kate M. Wassum, Ingrid C. Cely, Dr. Sean B. Ostlund, Dr. Nigel T. Maidment, Dr. Bernard W. Balleine
Charles Drew University of Medicine and Science4th Annual Drug Abuse Research SymposiumSeptember 26th 2008
Endogenous Opioid Regulation of Goal-Directed and Habitual Behavior
NAc NAs
DMS DLS
PFC
VTA
VP
CeN
MDT
Incentive Value
Opioid Receptors
How and Where are Opioid Receptors Involved in Goal-Directed Behavior?
How are opioid receptors in the basolateral amygdala, ventral pallidum and nucleus accumbens shell involved in affective and incentive value aspects of reward-related behavior?
BLA
Parsing Reward during Goal-Directed Instrumental Behavior
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Hungry Sated
Motivational State
Ext
inct
ion
Res
po
nse
R
ate
Reduction in responding without ever experiencing the incentive value change.
• Reward PalatabilityAffective component of reward consumption. ‘Liking’Reflected in taste reactivity or licking frequency.
• Incentive ValueThe relative significance of a specific reward outcome that is used to drive reward seeking. ‘How much a rat thinks the outcome of his actions is worth’
• General Motivational ArousalThe animal’s general drive towards all rewards.
Parsing Reward: Heterogeneous Seeking-Taking Chain with Lickometer
SeekingResponse rate changes only after incentive learning Incentive Value
TakingResponse rate changes before consumptionGeneral Motivational Arousal
Outcome DeliveryMeasure licking frequencywith contact lickometerReward Palatability
(Balleine 1995, Corbit and Balleine 2003, Balleine and Killcross 2006)
Assessing Opioid Involvement in Reward Palatability and Incentive Learning
Test Day 1: ½ Control group ½ Hungry group Naloxone (1µg) or Vehicle central infusions (BLA, NAs, VP)
Freely Administered Sucrose
Test Day 2: Chain Extinction Test Same hunger state, off drug
Training: Heterogeneous Seeking-Taking Chain 2 hours food deprivation
How much do the hungry animals ‘like’ the outcome?Does naloxone infused into the BLA, NAs or VP alter reward palatability?
Did the incentive value of the outcome change and does this change behavior?Does opioid receptor blockade in BLA, NAs or VP block incentive learning?
0255075
100125150175200225
ExtinctionDay 2: Off Drug
Vehicle Naloxone
* *
2hr23hr
See
kin
g %
Bas
elin
e
012345678
2hr23hr
*
Vehicle Naloxone
Palatability AnalysisDay 1: Intra-NAs Naloxone or Vehicle
*
Lic
ks/S
eco
nd
Endogenous opioids in the NAs are important for the expression of outcome palatability, but not assignment of incentive value
Intra-NAs naloxone blocks deprivation induced increase in outcome palatability
Nucleus Accumbens Shell
Intra-NAs naloxone does not effect incentive learning
0
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350
Vehicle Naloxone
*
**
2hr23hr
ExtinctionDay 2: Off Drug
See
kin
g %
Bas
eli
ne
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2hr23hr
*
Vehicle Naloxone
Palatability AnalysisDay 1: Intra-VP Naloxone or Vehicle
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Lic
ks
/Sec
on
dEndogenous opioids in the VP are important for the expression of outcome palatability, but not assignment of incentive value
Intra-VP naloxone blocks deprivation-induced increases in outcome palatability
Ventral Pallidum
Intra-VP naloxone does not effect incentive learning
0
50
100
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350
** *
Vehicle Naloxone
ExtinctionDay 2: Off Drug
See
kin
g %
Bas
eli
ne
Incentive Learning
Endogenous opioids in the BLA modulate the assignment of incentive value independent from outcome palatability
Basolateral Amygdala
Intra-BLA naloxone does not affect expression of outcome palatability
Blockade of opioid receptors in the BLA blocks encoding of incentive value
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1
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2hr23hr
**
Vehicle Naloxone
Palatability AnalysisDay 1: Intra-BLA Naloxone or Vehicle
Lic
ks/
Sec
on
d
0
50
100
150
200
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300
350
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Re-exposure Drug/Test DrugV
eh
icle
/V
eh
icle
Nal
oxon
e/V
eh
icle
Nal
oxon
e/N
alox
one
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hic
le/
Nal
oxon
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ExtinctionDay 2: On Drug
See
kin
g %
Bas
eli
ne
Blockade of opioid receptors in the BLA does not affect the retrieval of incentive value
• Reward palatability and outcome-specific incentive value are dissociable and independent aspects of goal-directed behavior
• Reward palatability and outcome-specific incentive value require opioid receptors
• Opioid receptors in the VP and NAs are important for expression of reward palatability, but not for incentive value
• Opioid receptors in the BLA are important for encoding, but not retrieving incentive value independent of reward palatability
Role of Endogenous Opioids in Goal-Directed Reward Seeking
Goal-Directed v Habitual BehaviorGoal-directed Actions
Reward Value-DependentAction-Outcome Learning
Habitual Responses
Reward Value-IndependentStimulus-Response Learning
Endogenous Opioid Peptides are involved in Reward Value
Does endogenous opioid disruption prevent action control by reward value and force habitual responding?
Devalue
Producing and Testing for Goal-Directed or Habitual Behavior
Over-trained Context500 Action-Outcome
Low-Trained Context50 Action-Outcome
Test (off drug)
OR
Naloxone/Vehicle
Does endogenous opioid blockade during learning alter goal-directed learning and force habitual responses?
Non Dev Non Dev Non Dev0
10
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Over-trainedContext
Low-TrainedContext
Vehicle Naloxone
*
Res
po
nse
Rat
e %
Bas
elin
e
Blockade of Opioid Receptors during Training Mimics Overtraining: Produces Habitual Behavior
Within-Subjects Rats show Goal-Directed behavior in one Context and Habitual Behavior in Naloxone-Paired Context
Test
OR
NaloxoneVehicle
Is opioid blockade-induced habitual behavior context specific?Does immediate opioid receptor blockade induce habitual behavior?
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Non Dev Non DevVehicle Naloxone
Vehicle Context
**
Acute Drug On Test
Res
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Rat
e %
Bas
elin
e
0
5
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Non Dev Non DevVehicle Naloxone
Naloxone Context
Acute Drug On Test
Res
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Rat
e %
Bas
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e
Conclusions
• Intact endogenous opioid system is necessary for normal goal-directed learning– Endogenous opioids in the VP and NAs important for expression of
palatability, but not reward seeking– Endogenous opioids in the BLA important for the encoding, but not
the retrieval of incentive value, independent from palatability
• Blockade of opioid receptors during learning results in inability of actions to be modulated by negative changes in outcome value
• Potential mechanism by which drugs of abuse may, by compromising the endogenous opioid system, render drug seeking actions inflexible to the value of their outcome
Acknowledgements • Dr. Nigel Maidment • Dr. Bernard Balleine
• Dr. Sean Ostlund• Dr. Robert Brown• Dr. Neil Winterbauer
• ***Ingrid Cely*** • Matt Maga• Hoa Lam• Larry Ackerson