Dopaminergic Modulation of Risky Decision-Making

Simon et. al., Dopaminergic Modulation of Risky Decision-Making, The Journal of Neuroscience, November 30, 2011 • 31(48):17460 –17470

Rewards Risks

Presented by Terry Dunlop

In this study, Simon says: Risky decision-making “involves choices between small “safe” rewards and large “risky” rewards accompanied by adverse consequences”.

What is Risky Decision-Making?Decision making – cognitive processes resulting in the selection of a course of action among several alternative scenarios. Every decision making process produces a final decision that can be an action or an opinion of choice.

Risky-Decision Making - Rewarding outcomes are accompanied by some degree of risk or adverse consequences.

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Next: Hypothetical risky-decision making scenarios

Risky-Decision MakingSimon et. al.(2011)

RiskReward

wikipedia.org/wiki/Decision_making

BrowniesFree Pizza

Risky Decision-Making Scenario 1

Rewarding Outcomes1.Signing autographs for the undergrad Biology students2.Free Brownies3.Boulder climbing with Mark Twight.

Risky Outcomes1.Late for Lab – Rat experiments failed. 2.Bad review as a Doctoral student.

Hey Justin, come climb!

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RiskReward

Brownies

Free Pizza

Risky Decision-Making Scenario 2

Rewarding Outcomes1.Signing up grad students for seminar class 2.Free Brownies/Pizza 3.Hump Back Pink Salmon

Risky Outcomes1.Late for Class – Students may leave after 15 minutes

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RiskReward

Risky Decision-Making Scenario 3

Rewarding Outcomes1.Signing autographs for the undergrad students – ego reward.2.Free Brownies/Pizza – Taste/food reward. 3.Check out the Woolly Mammoth– Interest, Passion reward.

Risky Outcomes1.Late for Class – Anxiety and Image. 2.Bad review as a Doctoral student. Jeopardize scholarship.3.Late for class, must speed to get there on time. Get a speeding ticket

BrowniesFree Pizza

Need Help Ask Alice

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RewardRisk

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Dopaminergic PathwaysVTA = Pleasure reward signals

http://en.wikipedia.org/wiki/File:Dopamine_Pathways.png

Side View

Underside

Simon et. al.(2011)

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DopamineA neurotransmitter responsible for reward-driven learning.

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Simon et. al.(2011)

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Dopamine D1 and D2

Simon study uses:

D1 Receptor - found within the neostriatum, nucleus accumbens and substantia nigra. Agonist - SKF81297 (Benzazepine derivative)

Antagonist –SCH23390 (Benzazepine derivative)

D2 Receptor – found in the pituitary, striatum, limbic system and the substantia nigra.

Agonist - Bromocriptine Mesylate Antagonist - Eticlopride Hydrochloride

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Risky Decision-Making Task (RDT)

Rat Boot Camp:

Risky Decision Tasks - Rats were trained to press a single lever to receive a single food pellet.

Criterion of 50 lever presses in 30 min, rats were then trained on the opposite lever under the same criterion.

Testing : RDT took place in standard rat behavioral test chambers (Coulbourn Instruments) housed within sound attenuating cubicles.

Experiment 1 = Long-Evans rats (n 12, 275–300 g) Experiment 2 = Long-Evans rats (n 18, 275–300 g)

RewardRisk

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Experiment 1

Rats took 21 sessions to achieve stable performance (at 0.35 mA shock intensity)

5 days no drugs, 8 days with drugs, (1,3,5,7 adm.)

1 food pellet (the small safe reward) delivered immediately 3 food pellets (the large risky reward) with had a possible 1 s footshock to each trial block.

The probability of footshock accompanying the large reward was set at 0% during the first 18-trial block. In subsequent 18-trial blocks, the probability of footshock increased to 25, 50, 75, and 100%.

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Experiment 1

D2- like receptor activation modulates risky decision-making. During the Risky Decision-making Task, rats were given choices between a small, safe food reward and a large food reward associated with risk of punishment. Each sessionconsisted of 5 blocks of 10 free-choice trials, with punishment probability increasing with each consecutive block.

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Neither a D1-like agonist (SKF81297) nor antagonist (SCH23390) had any effect on risk-taking.

Simon et. al.(2011)

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Experiment 1

Bromocriptine had a dose-dependent effect on risk-taking, shifting preference away from the large, risky reward. Eticlopride had no effect on risk-taking.

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Experiment 1Reward

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To confirm the D2-like receptor signaling in reducing risk-taking, the effects of coadministration of either the D1- or D2-like antagonist with amphetamine were examined.

Results: D2- like receptor blockade eliminates the effects of amphetamine on risky decision-making.

These data indicates that D2-like receptor activation is necessary for amphetamine to reduce riskyChoice.Note: Both drug combinations (as well as bromocriptine) increased

the number of omissions of forced choice trials. Althoughthis may have reduced the number of shocks experienced by therats during these trials, it would not have altered the probabilitiesof receiving shocks on the remaining (completed) trials, andhence, it is unlikely that these omissions significantly affectedperformance on the free-choice trials.

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Experiment 2 Behavioral DifferencesReward

Performance in the Risky Decision-making Task of rats used in Experiments 2 and 3.a = Risky Decision-making Task group, mean SEM. b = Individual variability of risky decision-making. Each line represents data from a single rat. c = Rats were divided into three groups based on risky decision-making performance: risk-taking (n5), moderate (n7), and risk-averse (n6).

*Data points in each figure represent the means (SEM) across the final 5 sessions of testing.

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Experiment 3RewardRisk

Hybridization of radiolabeled D1 and D2 mRNA in prefrontal cortex and striatum. Images from film autoradiogramsshow D1 (a, c) and D2 (b, d) receptor mRNA expression in coronal sections through the prefrontal cortex and striatum.

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D1 receptor mRNA expression and risky decision-making

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No significant relationship between risky decision-making and D1 expression in a,b,d,e.

Positive correlationsHigh D1 expression predicted high risk-taking in graph c, f.

All graphs p < 0.05, Tukey’s HSD post hoc test.

Risky-Decision Making Simon et. al.(2011)

Reward

RiskReward

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D2 receptor mRNA expression in prefrontal cortex and striatum

High levels of D2 expression predicted either high or low risk-taking

Low D2 expression predicting high or low risk-taking

No relationships in risky-decision making.

Negatively predicted risky decision-making: lower levels of hybridizationpredicted greater risk-taking

No relationships in risky-decision making.

No relationships in risky-decision making.

All graphs p < 0.05, Tukey’s HSD post hoc test.Risky-Decision Making

Simon et. al.(2011)

RiskReward

Risky decision-making is attenuated by D2-like (but not D1-like) receptor activation.

Stable phenotypes of preference for small safe versus large risky rewards is related to both D1 and D2 receptor mRNA expression in specific brain regions.

Dopamine signaling through distinct receptor classes in a network of corticostriatal brain regions as a critical modulator of decision-making under conditions of risk of adverse consequences.

Choice was likely not mediated solely by sensitivity to pain, but instead by a separate reward discounting process that reflects willingness to risk punishment. In rats, interactions between D1 receptor activity within the anterior cingulate cortex (ACC) and the core of the nucleus accumbens mediate decisions to expend greater effort to obtain larger rewards. (Hauber and Sommer, 2009).

Results and Implications

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Examples of Dopamine Roles

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Too Much Dopamine Frontal Lobe:

Overly suspicious personalityParanoiaInhibit social interactionLessens pain and increases pleasureEye blink rate increasesOCDNasal StuffinessAutonomic dysregulationDroopy EyelidsADD/ADHDPediatric Neurotransmitter Deficiency Disorders

Risky-Decision Making

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Compromised Dopamine:

Parkinson disease Incoherent thought (schizophrenia)Poor working memoryBasil ganglia show they are critical for executing smooth and controlled movements.DepressionEye blink rate decreases.

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Consider This!

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To move on or not to move on, that is the question?

Reward Dopamine for Thought?

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Haynes and colleagues show that several seconds before we consciously make a decision, its outcome can be predicted from unconscious activity in the brain, up to 7 seconds ahead of time. Max-Planck-Gesellschaft (2008)

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Rewards RiskReferences

Amen, D. (2011). How brain SPECT imaging can help with ADHD/ADD. Retrieved from http://www.amenclinics.com/clinics/information/ways-we-can-help/adhd-add

Heijtz RD, Kolb B, Forssberg H (2007). "Motor inhibitory role of dopamine D1 receptors: implications for ADHD" (PDF). Physiol Behav 92 (1–2): 155–160. doi:10.1016/j.physbeh.2007.05.024. PMID 17585966

Max-Planck-Gesellschaft (2008, April 14). Decision-making May Be Surprisingly Unconscious Activity. ScienceDaily. Retrieved February 22, 2012, from http://www.sciencedaily.com /releases/2008/04/080414145705.htm

Simon et. al.(2011), Dopaminergic Modulation of Risky Decision-Making, The Journal of Neuroscience, November 30, 2011 • 31(48):17460 –17470

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