Dopaminergic Modulation of Risky Decision-Making

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Dopaminergic Modulation of Risky Decision-Making
Presented by Terry Dunlop
Simon et. al., Dopaminergic Modulation of Risky
Decision-Making, The Journal of Neuroscience,
November 30, 2011 31(48)17460 17470
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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.
In this study, Simon says Risky decision-making
involves choices between small safe rewards
and large risky rewards accompanied by adverse
consequences.
Next Hypothetical risky-decision making scenarios
wikipedia.org/wiki/Decision_making

• Simon et. al.(2011)

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Risky Decision-Making Scenario 1
Hey Justin, come climb!

• Rewarding Outcomes
• Signing autographs for the undergrad Biology
  students
• Free Brownies
• Boulder climbing with Mark Twight.
• Risky Outcomes
• Late for Lab Rat experiments failed.
• Bad review as a Doctoral student.

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Risky Decision-Making Scenario 2

• Rewarding Outcomes
• Signing up grad students for seminar class
• Free Brownies/Pizza
• Hump Back Pink Salmon
• Risky Outcomes
• Late for Class Students may leave after 15
  minutes

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Risky Decision-Making Scenario 3
Want
We
Dave
Need Help Ask Alice

• Rewarding Outcomes
• Signing autographs for the undergrad students
  ego reward.
• Free Brownies/Pizza Taste/food reward.
• Check out the Woolly Mammoth Interest, Passion
  reward.
• Risky Outcomes
• Late for Class Anxiety and Image.
• Bad review as a Doctoral student. Jeopardize
  scholarship.
• Late for class, must speed to get there on time.
  Get a speeding ticket

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Dopaminergic Pathways
VTA Pleasure reward signals
Side View
Underside
http//en.wikipedia.org/wiki/FileDopamine_Pathway
s.png
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Dopamine
A neurotransmitter responsible for reward-driven
learning.

• 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

• Simon et. al.(2011)

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Risky Decision-Making Task (RDT)
Experiment 1 Long-Evans rats (n 12, 275300
g) Experiment 2 Long-Evans rats (n 18,
275300 g)
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.

• Simon et. al.(2011)

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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.

• Simon et. al.(2011)

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Experiment 1
Neither a D1-like agonist (SKF81297) nor
antagonist (SCH23390) had any effect on
risk-taking.
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
session consisted of 5 blocks of 10 free-choice
trials, with punishment probability increasing
with each consecutive block.

• 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.

• Simon et. al.(2011)

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Experiment 1
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 risky Choice.
Note Both drug combinations (as well as
bromocriptine) increased the number of omissions
of forced choice trials. Although this may have
reduced the number of shocks experienced by
the rats during these trials, it would not have
altered the probabilities of receiving shocks on
the remaining (completed) trials, and hence, it
is unlikely that these omissions significantly
affected performance on the free-choice trials.

• Simon et. al.(2011)

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Experiment 2 Behavioral Differences
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.

• Simon et. al.(2011)

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Experiment 3
Hybridization of radiolabeled D1 and D2 mRNA in
prefrontal cortex and striatum. Images from film
autoradiograms show D1 (a, c) and D2 (b, d)
receptor mRNA expression in coronal sections
through the prefrontal cortex and striatum.

• Simon et. al.(2011)

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D1 receptor mRNA expression and risky
decision-making
No significant relationship between risky
decision-making and D1 expression in a,b,d,e.
Positive correlations High D1 expression
predicted high risk-taking in graph c, f.
All graphs p lt 0.05, Tukeys HSD post hoc test.

• Simon et. al.(2011)

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D2 receptor mRNA expression in prefrontal cortex
and striatum
Negatively predicted risky decision-making lower
levels of hybridization predicted greater
risk-taking
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.
No relationships in risky-decision making.
No relationships in risky-decision making.
All graphs p lt 0.05, Tukeys HSD post hoc test.

• Simon et. al.(2011)

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Results and Implications

• 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).

• Simon et. al.(2011)

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Examples of Dopamine Roles
Too Much Dopamine Frontal Lobe Overly
suspicious personality Paranoia Inhibit social
interaction Lessens pain and increases
pleasure Eye blink rate increases OCD Nasal
Stuffiness Autonomic dysregulation Droopy
Eyelids ADD/ADHD Pediatric Neurotransmitter
Deficiency Disorders
Compromised Dopamine Parkinson disease
Incoherent thought (schizophrenia) Poor working
memory Basil ganglia show they are critical for
executing smooth and controlled
movements. Depression Eye blink rate decreases.
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Consider This!
To move on or not to move on, that is the
question?
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Dopamine for Thought?

• 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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References
Amen, D. (2011). How brain SPECT imaging can help
with ADHD/ADD. Retrieved from http//www.amenclin
ics.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
(12) 155160. doi10.1016/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.c
om /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