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

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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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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?

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ExtinctionDay 2: Off Drug

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Palatability AnalysisDay 1: Intra-NAs Naloxone or Vehicle

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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

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Palatability AnalysisDay 1: Intra-VP Naloxone or Vehicle

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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

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ExtinctionDay 2: Off Drug

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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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Palatability AnalysisDay 1: Intra-BLA Naloxone or Vehicle

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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)

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Does endogenous opioid blockade during learning alter goal-directed learning and force habitual responses?

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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

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Is opioid blockade-induced habitual behavior context specific?Does immediate opioid receptor blockade induce habitual behavior?

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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