Abstract
Rationale
Reward-associated cues can promote maladaptive behavior, including risky decision-making in a gambling setting. A propensity for sign tracking over goal tracking—i.e., interaction with a reward-predictive cue rather than the site of reward—demonstrates an individual’s tendency to transfer motivational value to a cue. However, the relationship of sign tracking to risky decision-making remains unclear.
Objectives
To determine whether sign tracking predicts risky choice, we used a Pavlovian conditioned approach task to evaluate the tendency of male rats to sign track to a lever cue and then trained rats on a rodent gambling task (rGT) with win-associated cues. We also tested the effects of d-amphetamine, quinpirole (a D2/D3 receptor agonist), and PD128907 (a D3 receptor agonist) on gambling behavior in sign tracker and goal tracker individuals.
Results
Increased sign tracking relative to goal tracking was associated with suboptimal performance on the rGT, including decreased selection of the optimal choice, increased selection of a high-risk/high-reward option, and increased impulsive premature choices. Amphetamine increased choices of a low-risk/low-reward option at the expense of optimal and high-risk choices, whereas quinpirole and PD128907 had little effect on choice allocation, but reduced impulsivity. Drug effects were similar across sign tracker and goal tracker individuals.
Conclusions
Cue reactivity, as measured by sign tracking, is predictive and may be an important driver of risky and impulsive choices in a gambling setting laden with salient audiovisual cues. Evaluating an individual’s sign tracking behavior may be an avenue to predict vulnerability to pathological gambling and the efficacy of treatments.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahrens AM, Meyer PJ, Ferguson LM, Robinson TE, Aldridge JW (2016) Neural activity in the ventral pallidum encodes variation in the incentive value of a reward cue. J Neurosci 36:7957–7970. https://doi.org/10.1523/JNEUROSCI.0736-16.2016
Barrus MM, Cherkasova M, Winstanley CA (2016) Skewed by Cues? The motivational role of audiovisual stimuli in modelling substance use and gambling disorders. Curr Top Behav Neurosci 27:507–529. https://doi.org/10.1007/7854_2015_393
Barrus MM, Hosking JG, Zeeb FD, Tremblay M, Winstanley CA (2015) Disadvantageous decision-making on a rodent gambling task is associated with increased motor impulsivity in a population of male rats. J Psychiatry Neurosci 40:108–117
Barrus MM, Winstanley CA (2016) Dopamine D3 receptors modulate the ability of win-paired cues to increase risky choice in a rat gambling task. J Neurosci 36:785–794. https://doi.org/10.1523/JNEUROSCI.2225-15.2016
Blaes SL et al (2018) Monoaminergic modulation of decision-making under risk of punishment in a rat model. Behav Pharmacol 29:745–761. https://doi.org/10.1097/FBP.0000000000000448
Boakes RA (1977) Performance on learning to associate a stimulus with positive reinforcement. In: Davis H, Hurwitz HMB (eds) Operant-Pavlovian Interactions. Lawrence Erlbaum Associates, Hillsdale, NJ, pp pp. 67–97
Bossert JM, Marchant NJ, Calu DJ, Shaham Y (2013) The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research. Psychopharmacology 229:453–476. https://doi.org/10.1007/s00213-013-3120-y
Cain ME, Green TA, Bardo MT (2006) Environmental enrichment decreases responding for visual novelty. Behav Processes 73:360–366. https://doi.org/10.1016/j.beproc.2006.08.007
Carter BL, Tiffany ST (1999) Meta-analysis of cue-reactivity in addiction research. Addiction 94:327–340
Cavedini P, Riboldi G, Keller R, D’Annucci A, Bellodi L (2002) Frontal lobe dysfunction in pathological gambling patients. Biol Psychiatry 51:334–341
Chow JJ, Nickell JR, Darna M, Beckmann JS (2016) Toward isolating the role of dopamine in the acquisition of incentive salience attribution. Neuropharmacology 109:320–331. https://doi.org/10.1016/j.neuropharm.2016.06.028
Chow JJ, Smith AP, Wilson AG, Zentall TR, Beckmann JS (2017) Suboptimal choice in rats: incentive salience attribution promotes maladaptive decision-making. Behav Brain Res 320:244–254. https://doi.org/10.1016/j.bbr.2016.12.013
Colaizzi JM, Flagel SB, Joyner MA, Gearhardt AN, Stewart JL, Paulus MP (2020) Mapping sign-tracking and goal-tracking onto human behaviors. Neurosci Biobehav Rev 111:84–94. https://doi.org/10.1016/j.neubiorev.2020.01.018
Dalley JW, Mar AC, Economidou D, Robbins TW (2008) Neurobehavioral mechanisms of impulsivity: fronto-striatal systems and functional neurochemistry. Pharmacol Biochem Behav 90:250–260. https://doi.org/10.1016/j.pbb.2007.12.021
DeVito EE et al (2008) The effects of methylphenidate on decision making in attention-deficit/hyperactivity disorder. Biol Psychiatry 64:636–639. https://doi.org/10.1016/j.biopsych.2008.04.017
Di Ciano P, Cardinal RN, Cowell RA, Little SJ, Everitt BJ (2001) Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of pavlovian approach behavior. J Neurosci 21:9471–9477
Economidou D, Theobald DE, Robbins TW, Everitt BJ, Dalley JW (2012) Norepinephrine and dopamine modulate impulsivity on the five-choice serial reaction time task through opponent actions in the shell and core sub-regions of the nucleus accumbens. Neuropsychopharmacology 37:2057–2066. https://doi.org/10.1038/npp.2012.53
Ferland JN et al (2019) 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 39:1842–1854. https://doi.org/10.1523/JNEUROSCI.3477-17.2018
Ferland JN, Winstanley CA (2017) Risk-preferring rats make worse decisions and show increased incubation of craving after cocaine self-administration. Addict Biol 22:991–1001. https://doi.org/10.1111/adb.12388
Fitzpatrick CJ et al (2013) Variation in the form of Pavlovian conditioned approach behavior among outbred male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs goal-tracking. PLoS One 8:e75042. https://doi.org/10.1371/journal.pone.0075042
Flagel SB, Akil H, Robinson TE (2009) Individual differences in the attribution of incentive salience to reward-related cues: implications for addiction. Neuropharmacology 56(Suppl 1):139–148. https://doi.org/10.1016/j.neuropharm.2008.06.027
Flagel SB et al (2011) A selective role for dopamine in stimulus-reward learning. Nature 469:53–57. https://doi.org/10.1038/nature09588
Flagel SB et al (2010) An animal model of genetic vulnerability to behavioral disinhibition and responsiveness to reward-related cues: implications for addiction. Neuropsychopharmacology 35:388–400. https://doi.org/10.1038/npp.2009.142
Flagel SB, Watson SJ, Akil H, Robinson TE (2008) Individual differences in the attribution of incentive salience to a reward-related cue: influence on cocaine sensitization. Behav Brain Res 186:48–56. https://doi.org/10.1016/j.bbr.2007.07.022
Freels TG, Gabriel DBK, Lester DB, Simon NW (2020) Risky decision-making predicts dopamine release dynamics in nucleus accumbens shell. Neuropsychopharmacology 45:266–275. https://doi.org/10.1038/s41386-019-0527-0
Georgiou P, Zanos P, Bhat S, Tracy JK, Merchenthaler IJ, McCarthy MM, Gould TD (2018) Dopamine and stress system modulation of sex differences in decision making. Neuropsychopharmacology 43:313–324. https://doi.org/10.1038/npp.2017.161
Gillis ZS, Morrison SE (2019) Sign tracking and goal tracking are characterized by distinct patterns of nucleus accumbens activity. eNeuro 6 https://doi.org/10.1523/ENEURO.0414-18.2019
Grant LD, Bowling AC (2015) Gambling attitudes and beliefs predict attentional bias in non-problem gamblers. J Gambl Stud 31:1487–1503. https://doi.org/10.1007/s10899-014-9468-z
Hearst E, Jenkins HM (1974) Sign-tracking: the stimulus-reinforcer relation and directed action. Psychonomic Society, Austin, TX
Langdon AJ, Hathaway BA, Zorowitz S, Harris CBW, Winstanley CA (2019) Relative insensitivity to time-out punishments induced by win-paired cues in a rat gambling task. Psychopharmacology 236:2543–2556. https://doi.org/10.1007/s00213-019-05308-x
Lovic V, Saunders BT, Yager LM, Robinson TE (2011) Rats prone to attribute incentive salience to reward cues are also prone to impulsive action. Behav Brain Res 223:255–261. https://doi.org/10.1016/j.bbr.2011.04.006
Mabrouk OS, Han JL, Wong JT, Akil H, Kennedy RT, Flagel SB (2018) The in vivo neurochemical profile of selectively bred high-responder and low-responder rats reveals baseline, cocaine-evoked, and novelty-evoked differences in monoaminergic systems. ACS Chem Neurosci 9:715–724. https://doi.org/10.1021/acschemneuro.7b00294
Madayag AC, Stringfield SJ, Reissner KJ, Boettiger CA, Robinson DL (2017) Sex and adolescent ethanol exposure influence Pavlovian conditioned approach. Alcohol Clin Exp Res 41:846–856. https://doi.org/10.1111/acer.13354
McGinty VB, Lardeux S, Taha SA, Kim JJ, Nicola SM (2013) Invigoration of reward seeking by cue and proximity encoding in the nucleus accumbens. Neuron 78:910–922. https://doi.org/10.1016/j.neuron.2013.04.010
Meyer PJ, Lovic V, Saunders BT, Yager LM, Flagel SB, Morrow JD, Robinson TE (2012) Quantifying individual variation in the propensity to attribute incentive salience to reward cues. PLoS ONE 7:e38987. https://doi.org/10.1371/journal.pone.0038987
Mitchell MR, Vokes CM, Blankenship AL, Simon NW, Setlow B (2011) Effects of acute administration of nicotine, amphetamine, diazepam, morphine, and ethanol on risky decision-making in rats. Psychopharmacology 218:703–712. https://doi.org/10.1007/s00213-011-2363-8
Moreno M et al (2013) Divergent effects of D(2)/(3) receptor activation in the nucleus accumbens core and shell on impulsivity and locomotor activity in high and low impulsive rats. Psychopharmacology 228:19–30. https://doi.org/10.1007/s00213-013-3010-3
Morrison SE, Bamkole MA, Nicola SM (2015) Sign tracking, but not goal tracking, is resistant to outcome devaluation. Front Neurosci 9:468. https://doi.org/10.3389/fnins.2015.00468
Morrison SE, Nicola SM (2014) Neurons in the nucleus accumbens promote selection bias for nearer objects. J Neurosci 34:14147–14162. https://doi.org/10.1523/JNEUROSCI.2197-14.2014
Murch WS, Clark L (2016) Games in the brain: neural substrates of gambling addiction. Neuroscientist 22:534–545. https://doi.org/10.1177/1073858415591474
Nautiyal KM, Okuda M, Hen R, Blanco C (2017) Gambling disorder: an integrative review of animal and human studies. Ann N Y Acad Sci 1394:106–127. https://doi.org/10.1111/nyas.13356
Nicola SM (2010) The flexible approach hypothesis: unification of effort and cue-responding hypotheses for the role of nucleus accumbens dopamine in the activation of reward-seeking behavior. J Neurosci 30:16585–16600. https://doi.org/10.1523/JNEUROSCI.3958-10.2010
Olsen CM, Winder DG (2009) Operant sensation seeking engages similar neural substrates to operant drug seeking in C57 mice. Neuropsychopharmacology 34:1685–1694. https://doi.org/10.1038/npp.2008.226
Olshavsky ME, Shumake J, Rosenthal AA, Kaddour-Djebbar A, Gonzalez-Lima F, Setlow B, Lee HJ (2014) Impulsivity, risk-taking, and distractibility in rats exhibiting robust conditioned orienting behaviors. J Exp Anal Behav 102:162–178. https://doi.org/10.1002/jeab.104
Parkinson JA et al (2002) Nucleus accumbens dopamine depletion impairs both acquisition and performance of appetitive Pavlovian approach behaviour: implications for mesoaccumbens dopamine function. Behav Brain Res 137:149–163
Robinson TE, Flagel SB (2009) Dissociating the predictive and incentive motivational properties of reward-related cues through the study of individual differences. Biol Psychiatry 65:869–873. https://doi.org/10.1016/j.biopsych.2008.09.006
Rode AN, Moghaddam B, Morrison SE (2020) Increased goal tracking in adolescent rats is goal-directed and not habit-like. Front Behav Neurosci 13:291. https://doi.org/10.3389/fnbeh.2019.00291
Saunders BT, Robinson TE (2012) The role of dopamine in the accumbens core in the expression of Pavlovian-conditioned responses. Eur J Neurosci 36:2521–2532. https://doi.org/10.1111/j.1460-9568.2012.08217.x
Saunders BT, Robinson TE (2013) Individual variation in resisting temptation: implications for addiction. Neurosci Biobehav Rev 37:1955–1975. https://doi.org/10.1016/j.neubiorev.2013.02.008
Schad DJ et al (2020) Dissociating neural learning signals in human sign- and goal-trackers. Nat Hum Behav 4:201–214. https://doi.org/10.1038/s41562-019-0765-5
Simon NW et al (2011) Dopaminergic modulation of risky decision-making. J Neurosci 31:17460–17470. https://doi.org/10.1523/JNEUROSCI.3772-11.2011
Singer BF et al (2016) Individual variation in incentive salience attribution and accumbens dopamine transporter expression and function. Eur J Neurosci 43:662–670. https://doi.org/10.1111/ejn.13134
Sokoloff P, Diaz J, Le Foll B, Guillin O, Leriche L, Bezard E, Gross C (2006) The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders. CNS Neurol Disord: Drug Targets 5:25–43. https://doi.org/10.2174/187152706784111551
Stopper CM, Khayambashi S, Floresco SB (2013) Receptor-specific modulation of risk-based decision making by nucleus accumbens dopamine. Neuropsychopharmacology 38:715–728. https://doi.org/10.1038/npp.2012.240
Stopper CM, Tse MT, Montes DR, Wiedman CR, Floresco SB (2014) Overriding phasic dopamine signals redirects action selection during risk/reward decision making. Neuron 84:177–189. https://doi.org/10.1016/j.neuron.2014.08.033
Tomie A, Grimes KL, Pohorecky LA (2008) Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse. Brain Res Rev 58:121–135. https://doi.org/10.1016/j.brainresrev.2007.12.003
Urcelay GP, Dalley JW (2012) Linking ADHD, impulsivity, and drug abuse: a neuropsychological perspective. Curr Top Behav Neurosci 9:173–197. https://doi.org/10.1007/7854_2011_119
Versaggi CL, King CP, Meyer PJ (2016) The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol. Psychopharmacology 233:2985–2997. https://doi.org/10.1007/s00213-016-4341-7
Winstanley CA, Clark L (2016) Translational models of gambling-related decision-making. Curr Top Behav Neurosci 28:93–120. https://doi.org/10.1007/7854_2015_5014
Yager LM, Robinson TE (2013) A classically conditioned cocaine cue acquires greater control over motivated behavior in rats prone to attribute incentive salience to a food cue. Psychopharmacology 226:217–228. https://doi.org/10.1007/s00213-012-2890-y
Zalocusky KA, Ramakrishnan C, Lerner TN, Davidson TJ, Knutson B, Deisseroth K (2016) Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making. Nature 531:642–646. https://doi.org/10.1038/nature17400
Zeeb FD, Robbins TW, Winstanley CA (2009) Serotonergic and dopaminergic modulation of gambling behavior as assessed using a novel rat gambling task. Neuropsychopharmacology 34:2329–2343. https://doi.org/10.1038/npp.2009.62
Acknowledgements
We would like to thank Nicholas Simon and Mary Torregrossa for their helpful comments on the manuscript.
Funding
This work was supported by an award from the International Center for Responsible Gaming (ICRG), an award from the University of Pittsburgh Medical Center Competitive Medical Research Fund (CMRF), and National Institutes of Health grant R03DA045913.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Swintosky, M., Brennan, J.T., Koziel, C. et al. Sign tracking predicts suboptimal behavior in a rodent gambling task. Psychopharmacology 238, 2645–2660 (2021). https://doi.org/10.1007/s00213-021-05887-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-021-05887-8