Risky decision-making predicts dopamine release dynamics in nucleus accumbens shell

Abstract

The risky decision-making task (RDT) measures risk-taking in a rat model by assessing preference between a small, safe reward and a large reward with increasing risk of punishment (mild foot shock). It is well-established that dopaminergic drugs modulate risk-taking; however, little is known about how differences in baseline phasic dopamine signaling drive individual differences in risk preference. Here, we used in vivo fixed potential amperometry in male Long-Evans rats to test if phasic nucleus accumbens shell (NACs) dopamine dynamics are associated with risk-taking. We observed a positive correlation between medial forebrain bundle-evoked dopamine release in the NACs and risky decision-making, suggesting that risk-taking is associated with elevated dopamine sensitivity. Moreover, “risk-taking” subjects were found to demonstrate greater phasic dopamine release than “risk-averse” subjects. Risky decision-making also predicted enhanced sensitivity to the dopamine reuptake inhibitor nomifensine, and elevated autoreceptor function. Importantly, this hyperdopaminergic phenotype was selective for risky decision-making, as delay discounting performance was not predictive of phasic dopamine release or dopamine supply. These data identify phasic NACs dopamine release as a possible therapeutic target for alleviating the excessive risk-taking observed across multiple forms of psychopathology.

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References

  1. 1.

    Simon NW, Gilbert RJ, Mayse JD, Bizon JL, Setlow B. Balancing risk and reward: a rat model of risky decision making. Neuropsychopharmacology. 2009;34:2208–2217.

  2. 2.

    Negus SS. Effects of punishment on choice between cocaine and food in rhesus monkeys. Psychopharmacology (Berl). 2005;181:244–252.

  3. 3.

    Verdejo-Garcia A, Chong TT, Stout JC, Yucel M, London ED. Stages of dysfunctional decision-making in addiction. Pharmacol Biochem Behav. 2018. https://doi.org/10.1016/j.pbb.2017.02.003.

  4. 4.

    Bechara A, Dolan S, Denburg N, Hindes A, Anderson SW, Nathan PE. Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia. 2001;39:376–389.

  5. 5.

    Brand M, Roth-Bauer M, Driessen M, Markowitsch HJ. Executive functions and risky decision-making in patients with opiate dependence. Drug Alcohol Depend. 2008;97:64–72.

  6. 6.

    Brevers D, Bechara A, Cleeremans A, Kornreich C, Verbanck P, Noël X. Impaired decision-making under risk in individuals with alcohol dependence. Alcohol Clin Exp Res. 2014;38:1924–1931.

  7. 7.

    Simon NW, Montgomery KS, Beas BS, Mitchell MR, LaSarge CL, Mendez IA, et al. Dopaminergic modulation of risky decision-making. J Neurosci. 2011;31:17460–17470.

  8. 8.

    Mitchell MR, Vokes CM, Blankenship AL, Simon NW, Setlow B. Effects of acute administration of nicotine, amphetamine, diazepam, morphine, and ethanol on risky decision-making in rats. Psychopharmacology (Berl). 2011;218:703–712.

  9. 9.

    Mitchell MR, Weiss VG, Beas BS, Morgan D, Bizon JL, Setlow B. Adolescent risk taking, cocaine self-administration, and striatal dopamine signaling. Neuropsychopharmacology. 2014;39:955–962.

  10. 10.

    Gabriel DBK, Freels TG, Setlow B, Simon NW. Risky decision-making is associated with impulsive action and sensitivity to first-time nicotine exposure. Behav Brain Res. 2019;359:579–588.

  11. 11.

    Olshavsky ME, Shumake J, Rosenthal AA, Kaddour-Djebbar A, Gonzalez-Lima F, Setlow B, et al. Impulsivity, risk-taking, and distractibility in rats exhibiting robust conditioned orienting behaviors. J Exp Anal Behav. 2014;102:162–178.

  12. 12.

    Floresco SB, West AR, Ash B, Moorel H, Grace AA, Moore H, et al. Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat Neurosci. 2003;6:968–973.

  13. 13.

    Schultz W. Predictive reward signal of dopamine neurons. J Neurophysiol. 1998;80:1–27.

  14. 14.

    Wise RA, Bozarth MA. Brain mechanisms of drug reward and euphoria. Psychiatr Med. 1985;3:445–460.

  15. 15.

    Robinson TE, Berridge KC. The neural basis of drug craving: an incentive salience theory of addiction. Brain Res Rev. 1993;8:247–291.

  16. 16.

    Ikemoto S, Panksepp J. The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res Rev. 1999;31:6–41.

  17. 17.

    Saddoris MP, Sugam JA, Stuber GD, Witten IB, Deisseroth K, Carelli RM. Mesolimbic dopamine dynamically tracks, and is causally linked to, discrete aspects of value-based decision making. Biol Psychiatry. 2015;77:903–911.

  18. 18.

    Benoit-Marand M, Suaud-Chagny M-F, Gonon F. Presynaptic regulation of extracellular dopamine as studied by continuous amperometry in anesthetized animals. In: Electrochemical Methods for Neuroscience. (eds Michael AC, Borland LM) Chapter 3, CRC Press/Taylor & Francis; 2007.

  19. 19.

    Holloway ZR, Freels TG, Comstock JF, Nolen HG, Sable HJ, Lester DB. Comparing phasic dopamine dynamics in the striatum, nucleus accumbens, amygdala, and medial prefrontal cortex. Synapse. 2018;73:e22074.

  20. 20.

    Mittleman G, Call SB, Cockroft JL, Goldowitz D, Matthews DB, Blaha CD. Dopamine dynamics associated with, and resulting from, schedule-induced alcohol self-administration: analyses in dopamine transporter knockout mice. Alcohol. 2011;45:325–339.

  21. 21.

    Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai C, Finkelstein J, et al. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature. 2013;493:537–541.

  22. 22.

    Garavan H, Hester R. The role of cognitive control in cocaine dependence. Neuropsychol Rev. 2007;17:337–345.

  23. 23.

    Perry JL, Carroll ME. The role of impulsive behavior in drug abuse. Psychopharmacology. 2008;200:1–26.

  24. 24.

    Bickel WK, Johnson MW, Koffarnus MN, MacKillop J, Murphy JG. The behavioral economics of substance use disorders: reinforcement pathologies and their repair. Annu Rev Clin Psychol. 2014;10:641–677.

  25. 25.

    Simon NW, Mendez IA, Setlow B. Cocaine exposure causes long-term increases in impulsive choice. Behav Neurosci. 2007;121:543–549.

  26. 26.

    Orsini CA, Blaes SL, Setlow B, Simon NW. Recent updates in modeling risky decision-making in rodents. Methods Mol Biol. 2019;2011:79–92

  27. 27.

    Simon NW, Setlow B. Modeling risky decision making in rodents. Methods Mol Biol. 2012;829:165–175.

  28. 28.

    Sabeti J, Gerhardt GA, Zahniser NR. Chloral hydrate and ethanol, but not urethane, alter the clearance of exogenous dopamine recorded by chronoamperometry in striatum of unrestrained rats. Neurosci Lett. 2003;343:9–12.

  29. 29.

    Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 3rd ed. San Diego: Acad Press; 1997.

  30. 30.

    Dugast C, Suaud-Chagny MF, Gonon F. Continuous in vivo monitoring of evoked dopamine release in the rat nucleus accumbens by amperometry. Neuroscience. 1994. https://doi.org/10.1016/0306-4522(94)90466-9.

  31. 31.

    Fielding JR, Rogers TD, Meyer AE, Miller MM, Nelms JL, Mittleman G, et al. Stimulation-evoked dopamine release in the nucleus accumbens following cocaine administration in rats perinatally exposed to polychlorinated biphenyls. Toxicol Sci. 2013;136:144–153.

  32. 32.

    Hyland BI, Reynolds JNJ, Hay J, Perk CG, Miller R. Firing Modes of Midbrain Dopamine Cells in the freely moving rat. Neuroscience. 2002;114:475–492.

  33. 33.

    Tsai H-C, Zhang F, Adamantidis A, Stuber GD, Bonci A, Lecea Lde, et al. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009;324:1080–1084.

  34. 34.

    Carboni E, Imperato A, Perezzani L, Di Chiara G. Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats. Neuroscience. 1989;28:653–661.

  35. 35.

    Prater WT, Swamy M, Beane MD, Lester DB. Examining the effects of common laboratory methods on the sensitivity of carbon fiber electrodes in amperometric recordings of dopamine. J Behav Brain Sci. 2018;8:117–125.

  36. 36.

    Michael DJ, Wightman RM. Electrochemical monitoring of biogenic amine neurotransmission in real time. J Pharm Biomed Anal. 1999;19:33–46.

  37. 37.

    MacQueen J. Some methods for classification and analysis of multivariate observations. In Fifth Berkeley Symp. Math. Stat. Probab. Statistical Laboratory, University of California, Berkeley, (1967).

  38. 38.

    Freels TG, Lester DB, Cook MN. Arachidonoyl serotonin (AA-5-HT) modulates general fear-like behavior and inhibits mesolimbic dopamine release. Behav Brain Res. 2019;362:140–151.

  39. 39.

    Flagel SB, Clark JJ, Robinson TE, Mayo L, Czuj A, Willuhn I, et al. A selective role for dopamine in stimulus-reward learning. Nature. 2011;469:53–59.

  40. 40.

    Benoit-Marand M, Jaber M, Gonon F. Release and elimination of dopamine in vivo in mice lacking the dopamine transporter: functional consequences. Eur J Neurosci. 2000;12:2985–2992.

  41. 41.

    Shimp KG, Mitchell MR, Beas BS, Bizon JL, Setlow B. Affective and cognitive mechanisms of risky decision making. Neurobiol Learn Mem. 2015;117:60–70.

  42. 42.

    Millan MJ, Brocco M, Papp M, Serres F, La Rochelle CD, Sharp T, et al. S32504, a novel naphtoxazine agonist at dopamine D3/D2 receptors: III. Actions in models of potential antidepressive and anxiolytic activity in comparison with ropinirole. J Pharm Exp Ther. 2004;309:936–950.

  43. 43.

    Bali A, Jaggi AS. Electric foot shock stress: a useful tool in neuropsychiatric studies. Rev Neurosci. 2015;26:655–677.

  44. 44.

    Everitt BJ, Robbins TW. Drug addiction: updating actions to habits to compulsions ten years on. Annu Rev Psychol. 2016;67:23–50.

  45. 45.

    Dalley JW, Robbins TW. Fractionating impulsivity: neuropsychiatric implications. Nat Rev Neurosci. 2017;18:158–171.

  46. 46.

    Robbins TW. The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl). 2002;163:362–380.

  47. 47.

    Zalocusky KA, Ramakrishnan C, Lerner TN, Davidson TJ, Knutson B, Deisseroth K. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. Nature. 2016;531:642–646.

  48. 48.

    Pattij T, Janssen MCW, Vanderschuren LJMJ, Schoffelmeer ANM, van Gaalen MM. Involvement of dopamine D1 and D2 receptors in the nucleus accumbens core and shell in inhibitory response control. Psychopharmacology (Berl). 2007;191:587–598.

  49. 49.

    Besson M, Belin D, McNamara R, Theobald DEH, Castel A, Beckett VL, et al. Dissociable control of impulsivity in rats by dopamine D2/3 receptors in the core and shell subregions of the nucleus accumbens. Neuropsychopharmacology. 2010;35:560–569.

  50. 50.

    Dalley JW, Fryer TD, Brichard L, Robinson ESJ, Theobald DEH, Laane K, et al. Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science. 2007;315:1267–1270.

  51. 51.

    Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ. High impulsivity predicts the switch to compulsive cocaine-taking. Science. 2008;320:1352–1356.

  52. 52.

    Orsini CA, Moorman DE, Young JW, Setlow B, Floresco SB. Neural mechanisms regulating different forms of risk-related decision-making: Insights from animal models. Neurosci Biobehav Rev. 2015;58:147–167.

  53. 53.

    St. Onge JR, Ahn S, Phillips AG, Floresco SB. Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus accumbens during risk-based decision making. J Neurosci. 2012;32:16880–16891.

  54. 54.

    Fiorillo CD, Tobler PN, Schultz W. Discrete coding of reward dopamine neurons. Science. 2003;299:1898–1902.

  55. 55.

    Stopper CM, Tse MTL, Montes DR, Wiedman CR, Floresco SB. Overriding phasic dopamine signals redirects action selection during risk/reward decision making. Neuron. 2014;84:177–189.

  56. 56.

    Sugam JA, Saddoris MP, Carelli RM. Nucleus accumbens neurons track behavioral preferences and reward outcomes during risky decision making. Biol Psychiatry. 2014;75:807–816.

  57. 57.

    Stopper CM, Floresco SB. Contributions of the nucleus accumbens and its subregions to different aspects of risk-based decision making. Cogn Affect Behav Neurosci. 2011;11:97–112.

  58. 58.

    de Jong JW, Afjei SA, Pollak Dorocic I, Peck JR, Liu C, Kim CK, et al. A neural circuit mechanism for encoding aversive stimuli in the mesolimbic dopamine system. Neuron. 2019. https://doi.org/10.1016/j.neuron.2018.11.005.

  59. 59.

    Badrinarayan A, Wescott SA, CMV Weele, Saunders BT, Couturier BE, Maren S, et al. Aversive stimuli differentially modulate real-time dopamine transmission dynamics within the nucleus accumbens core and shell. J Neurosci. 2012;32:15779–15790.

  60. 60.

    Piantadosi PT, Yeates DCM, Wilkins M, Floresco SB. Contributions of basolateral amygdala and nucleus accumbens subregions to mediating motivational conflict during punished reward-seeking. Neurobiol Learn Mem. 2017;140:92–105.

  61. 61.

    Simon NW, Beas BS, Montgomery KS, Haberman RP, Bizon JL, Setlow B. Prefrontal cortical–striatal dopamine receptor mRNA expression predicts distinct forms of impulsivity. Eur J Neurosci. 2013;37:1779–1788.

  62. 62.

    Ferland JN, Hynes TJ, Hounjet CD, Lindenbach D, Haar CV, Adams WK, et al. Prior exposure to salient win-paired cues in a rat gambling task increases sensitivity to cocaine self-administration and suppresses dopamine efflux in nucleus accumbens: support for the reward deficiency hypothesis of addiction. J Neurosci. 2019;39:1842–1854.

  63. 63.

    Gentry RN, Lee B, Roesch MR. Phasic dopamine release in the rat nucleus accumbens predicts approach and avoidance performance. Nat Commun. 2016;7:1–11.

  64. 64.

    Kuczenski R, Segal D. Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis. J Neurosci. 1989;9:2051–2065.

  65. 65.

    Mcelvain JS, Schenk JO. A multisubstrate mechanism of striatal dopamine uptake and its inhibition by cocaine. Biochem Pharm. 1992;43:2189–2199.

  66. 66.

    Wade TR, De Wit H, Richards JB. Effects of dopaminergic drugs on delayed reward as a measure of impulsive behavior in rats. Psychopharmacology (Berl). 2000;150:90–101.

  67. 67.

    van Gaalen MM, van Koten R, Schoffelmeer ANM, Vanderschuren LJMJ. Critical involvement of dopaminergic neurotransmission in impulsive decision making. Biol Psychiatry. 2006. https://doi.org/10.1016/j.biopsych.2005.06.005.

  68. 68.

    Winstanley CA, Theobald DEH, Dalley JW, Robbins TW. Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders. Neuropsychopharmacology. 2005;30:669–682.

  69. 69.

    Castrellon JJ, Seaman KL, Crawford JL, Young JS, Smith CT, Dang LC, et al. Individual differences in dopamine are associated with reward discounting in clinical groups but not in healthy adults. J Neurosci. 2019;39:321–332.

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Acknowledgements

We would like to thank Amber Woods, Haleigh Joyner, Samantha Morrison, Andrew Starnes, and Alan Rasheed for technical assistance.

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Correspondence to Nicholas W. Simon.

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Freels, T.G., Gabriel, D.B.K., Lester, D.B. et al. Risky decision-making predicts dopamine release dynamics in nucleus accumbens shell. Neuropsychopharmacol. 45, 266–275 (2020) doi:10.1038/s41386-019-0527-0

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