Dopaminergic Modulation of Risky Decision-Making

1. Presented by Terry Dunlop Dopaminergic Modulation of Risky Decision-Making Rewards Risks Simon et. al., Dopaminergic Modulation of Risky Decision-Making, The Journal of Neuroscience, November 30, 2011 • 31(48):17460 –17470

2. What is Risky Decision-Making? Risk Reward 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. Simon et. al.(2011) 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 Risky-Decision Making

3. Risky Decision-Making Scenario 1 Risk Reward Hey Justin, come climb! Free Pizza Brownies 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. Risky-Decision Making

4. Risky Decision-Making Scenario 2 Risk Reward Free Pizza Brownies 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 Risky-Decision Making

5. Risky Decision-Making Scenario 3 Risk Reward We Want Dave Free Pizza Need Help Ask Alice Brownies 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 Risky-Decision Making

6. Dopaminergic Pathways Risk Reward VTA = Pleasure reward signals Side View Underside http://en.wikipedia.org/wiki/File:Dopamine_Pathways.png Risky-Decision Making

7. Dopamine Risk Reward A neurotransmitter responsible for reward-driven learning. Simon et. al.(2011) Risky-Decision Making

8. Dopamine D1 and D2 Risk Reward 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) Risky-Decision Making

9. Risky Decision-Making Task (RDT) Risk Reward Experiment 1 = Long-Evans rats (n 12, 275–300 g) Experiment 2 = Long-Evans rats (n 18, 275–300 g) Rat Boot Camp: Simon et. al.(2011) 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. Risky-Decision Making

10. Experiment 1 Risk Reward 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) Risky-Decision Making

11. Experiment 1 Risk Neither a D1-like agonist (SKF81297) nor antagonist (SCH23390) had any effect on risk-taking. Reward Simon et. al.(2011) 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. Risky-Decision Making

12. Experiment 1 Risk Reward Simon et. al.(2011) Bromocriptine had a dose-dependent effect on risk-taking, shifting preference away from the large, risky reward. Eticlopride had no effect on risk-taking. Risky-Decision Making

13. Experiment 1 Risk Reward 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. Simon et. al.(2011) 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. Risky-Decision Making

14. Experiment 2 Behavioral Differences Reward Risk Simon et. al.(2011) 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. Risky-Decision Making

15. Experiment 3 Risk Reward 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) Risky-Decision Making

16. D1 receptor mRNA expression and risky decision-making Reward Risk Simon et. al.(2011) 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 < 0.05, Tukey’s HSD post hoc test. Risky-Decision Making

17. D2 receptor mRNA expression in prefrontal cortex and striatum Reward Risk 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 Simon et. al.(2011) 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 < 0.05, Tukey’s HSD post hoc test. Risky-Decision Making

18. Results and Implications Reward Risk • 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) Risky-Decision Making

19. Examples of Dopamine Roles Reward Risk 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. Risky-Decision Making

20. Consider This! Reward Risk To move on or not to move on, that is the question? Risky-Decision Making

21. Dopamine for Thought? Reward Risk • 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) Risky-Decision Making

22. References Risk Rewards 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 Behav92 (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 Risky-Decision Making