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Cited by 1,026Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesMemory and Neural Mechanisms

A selective role for dopamine in stimulus-reward learning

Open access
Flagel, Shelly B., Clark, Jeremy J., Robinson, Terry E., Mayo, Leah, Czuj, Alayna, Willuhn, Ingo, Akers, Christina A., Clinton, Sarah M. +2 more·2011·Nature
DOI 10.1038/nature09588PMC PMC3058375
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Abstract

Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus–reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus–reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus–reward learning that confers increased susceptibility to disorders of impulse control.

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Written from the paper’s full text.

TL;DR

Dopamine is not required for all forms of stimulus-reward learning; it selectively supports the attribution of incentive salience to reward cues. In rats, sign-trackers show increasing CS-evoked and decreasing US-evoked nucleus accumbens dopamine during Pavlovian conditioning, and dopamine antagonism prevents acquisition of sign-tracking but not goal-tracking conditioned responses.

Key findings

  • Systemic flupenthixol attenuated performance of the conditioned response in both bHRs and bLRs, but only bHRs failed to acquire a sign-tracking CR when trained on drug; on drug-free session 8, bHRs still failed to show sign-tracking (P≤0.01 vs saline), whereas bLRs showed a fully developed goal-tracking CR (session 8 vs session 1, P≤0.0002; vs bLR saline, P≥0.6).
  • During acquisition, CS-evoked dopamine release increased in bHRs relative to unpaired controls (pairing × session: F(5,35)=4.58, P=0.003) but not bLRs (F(5,35)=0.94, P=0.46); trial-by-trial correlation with trial number was significant for bHR (r²=0.14, P<0.0001) but not bLR (r²=0.003, P=0.54), with different slopes (P=0.005) and higher CS-evoked dopamine in bHRs after acquisition (session six, P=0.04).
  • US-evoked dopamine release was lower after acquisition in bHRs (session six, P=0.002), and CS and US signals diverged in bHRs (stimulus × session: F(5,40)=5.47, P=0.0006) but not bLRs (F(5,40)=0.28, P=0.92).
  • Outbred rats reproduced the pattern: sign-trackers showed increased CS-evoked and decreased US-evoked dopamine during learning (stimulus × session: F(5,50)=4.43, P=0.002), whereas goal-trackers did not (F(5,40)=0.48, P=0.72); the lever-CS was also a more effective conditioned reinforcer in bHRs than bLRs (phenotype × group interaction for active nose pokes: F(1,33)=4.82, P=0.04).

Methods

  • Adult male Sprague-Dawley rats from a selective-breeding colony (bHR/bLR, generations S18–S22) and commercially obtained outbred rats underwent Pavlovian conditioning with a lever-CS paired with food; conditioned responses were classified as sign-tracking (approach lever-CS) or goal-tracking (approach food-tray).
  • Fast-scan cyclic voltammetry at carbon-fiber microelectrodes in the nucleus accumbens core measured phasic dopamine (scans every 100 ms, 10 Hz) during conditioning; recording sites were verified histologically.
  • Flupenthixol (i.p.) was given for performance (150, 300, or 600 μg/kg before sessions 9, 11, 13, counterbalanced with saline before sessions 8, 10, 12, 14) and for acquisition (225 μg/kg before sessions 1–7); main analyses used ANOVA/ANOVA with session as a continuous variable and correlations.

Limitations

  • Stated: the neural mechanisms underlying sign-tracking and goal-tracking behavior remain to be elucidated; the neurochemical data alone do not rule out the possibility that prediction-error signals are present in other dopamine terminal regions.
  • Stated: the post-acquisition flupenthixol finding needs cautious interpretation because of a non-specific effect on activity.
  • Evident from the text: the causal dopamine manipulation was systemic flupenthixol, and the sample was male rats (selectively bred plus outbred); no female or human data are reported.

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Integrity signals

Registry

Crossref · 10.1038/nature09588

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

15 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

0 of 39 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Systemic administration of flupenthixol, a nonspecific dopamine receptor antagonist, attenuated performance of the CR for both bHRs and bLRs.

    “Systemic administration of flupenthixol, a nonspecific dopamine receptor antagonist, attenuated performance of the CR for both bHRs and bLRs.”
    Quote in the paperSubstantial claim
  • Findingown data

    With training, bHRs came to rapidly approach and engage the lever-CS.

    “With training, bHRs came to rapidly approach and engage the lever-CS (Fig. 1a-b)”
    Quote in the paperNot a substantial claim
  • Findingown data

    The effect of flupenthixol on performance was clearly evident when the antagonist was administered during training.

    “This effect was clearly evident when the antagonist was administered during training (Fig. 4, sessions 1–7).”
    Quote in the paperSubstantial claim
  • Findingown data

    US-evoked dopamine release in the nucleus accumbens decreased during training in sign-trackers, but not in goal-trackers.

    “First, US-evoked dopamine release in the nucleus accumbens decreased during training in sign-trackers, but not in goal-trackers.”
    Quote in the paperSubstantial claim
  • Findingcitation

    In outbred rats where the baseline difference in responding does not exist, the lever-CS is a more effective conditioned reinforcer for sign-trackers than goal-trackers.

    “Moreover, in outbred rats where this baseline difference in responding does not exist, we have found similar results, indicating that the lever-CS is a more effective conditioned reinforcer for sign-trackers than goal-trackers13.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Boakes, R. in Operant-Pavlovian Interactions (eds Davis, H. & Hurwitz, H. M. B.) 67–97 (Erlbaum, 1977)

      Not checked in the free run.

  • May combine two claims. 33
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 4

  • May combine two claims.

    Findingown data

    Both bHRs and bLRs acquired their respective CRs as a function of training, as there was a significant effect of session for all measures of sign-tracking behavior for bHRs and of goal-tracking behavior for bLRs.

    “Both bHRs and bLRs acquired their respective CRs as a function of training, as there was a significant effect of session for all measures of sign-tracking behavior for bHRs (a-b; P≤0.0001), and of goal-tracking behavior for bLRs (c-d; P≤0.0001).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    US-evoked dopamine release also differed between bHR and bLR rats during training, but for this stimulus dopamine release was lower after acquisition in bHRs.

    “US-evoked dopamine release also differed between bHR and bLR rats during training (session x phenotype interaction: F(5,40) = 6.09, P = 0.0003), but for this stimulus dopamine release was lower after acquisition in bHRs (session six; P = 0.002; Fig. S4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The trial-by-trial correlation between CS-evoked dopamine release and trial number was significant for bHR but not bLR rats, producing significantly different slopes and higher CS-evoked dopamine release in bHR rats after acquisition.

    “Indeed, the trial-by-trial correlation between CS-evoked dopamine release and trial number was significant for bHR (r2=0.14, P < 0.0001) but not bLR (r2=0.003, P=0.54) rats, producing significantly different slopes (P=0.005) and higher CS-evoked dopamine release in bHR rats after acquisition (Fig. S4, session six; P = 0.04).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    During the acquisition of conditioned approach, CS-evoked dopamine release increased in bHR rats relative to unpaired controls, but there was no such effect in bLRs.

    “During the acquisition of conditioned approach, CS-evoked dopamine release (Fig. 2, Fig. S3) increased in bHR rats relative to unpaired controls (pairing x session interaction: F(5,35) = 4.58, P = 0.003), but there was no such effect in bLRs (Fig. 2, Fig. S3; pairing x session interaction: F(5,35) = 0.94, P = 0.46).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    bHR rats that underwent Pavlovian training in the presence of a dopamine receptor antagonist did not acquire a sign-tracking CR, consistent with previous reports; however, dopamine antagonism had no effect on learning a goal-tracking CR in bLR rats.

    “Third, bHR rats that underwent Pavlovian training in the presence of a dopamine receptor antagonist did not acquire a sign-tracking CR, consistent with previous reports24; however, dopamine antagonism had no effect on learning a goal-tracking CR in bLR rats.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Clark, J. J. et al. Chronic microsensors for longitudinal, subsecond dopamine detection in behaving animals. Nature Methods 7, 126–129 (2010) source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    bHRs and bLRs learned their respective CRs at the same rate, as indicated by non-significant phenotype x session interactions for number of contacts and latency to approach.

    “Furthermore, bHRs and bLRs learned their respective CRs at the same rate, as indicated by analyses of variance in which session was treated as a continuous variable and the phenotypes were directly compared.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The CS and US signals diverge in bHR rats but not bLR rats.

    “The CS and US signals diverge in bHR rats (stimulus x session interaction: F(5,40) = 5.47, P = 0.0006; Fig. 2c) but not bLR rats (stimulus x session interaction: F(5,40) = 0.28, P = 0.92; Fig. 2f).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was an increase in CS-evoked and a decrease in US-evoked dopamine release during learning in outbred rats that learned a sign-tracking CR, but not in those that learned a goal-tracking CR.

    “Specifically, there was an increase in CS-evoked and a decrease in US-evoked dopamine release during learning in outbred rats that learned a sign-tracking CR (stimulus x session interaction: F(5,50) = 4.43, P = 0.002; Fig. 3d), but not in those that learned a goal-tracking CR (stimulus x session interaction: F(5,40) = 0.48, P = 0.72; Fig. 3f).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    When presentation of a lever-CS was paired with food delivery, both bHRs and bLRs developed a Pavlovian CR, but the topography of the CR was different in the two groups.

    “When presentation of a lever-CS was paired with food delivery both bHRs and bLRs developed a Pavlovian CR, but as we have described previously15, the topography of the CR was different in the two groups.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Stead, J. D. et al. Selective breeding for divergence in novelty-seeking traits: heritability and enrichment in spontaneous anxiety-related behaviors. Behav. Genet. 36, 697–712 (2006) source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The lever-CS was a more effective conditioned reinforcer in bHR than bLR animals, as indicated by a significant phenotype x group interaction for active nose pokes.

    “However, the lever-CS was a more effective conditioned reinforcer in bHR than bLR animals, as indicated by a significant phenotype x group interaction for active nose pokes (F(1,33)=4.82, P=0.04), which controls for “basal” differences in nosepoke responding.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Flupenthixol had no effect on learning the CS-US association that lead to a goal-tracking CR, because on the drug-free session bLRs showed a fully developed goal-tracking CR.

    “In contrast, flupenthixol had no effect on learning the CS-US association that lead to a goal-tracking CR (P≥0.6 vs. saline, session 8; Fig. 4d-f), because on the drug-free session bLRs showed a fully developed goal-tracking CR—their session 8 performance differed significantly from their session 1 performance (P≤0.0002).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both conditioned bHRs and bLRs made more active than inactive nose pokes, and more active nose pokes than control groups that received pseudorandom presentations of the CS and the US.

    “Both conditioned bHRs and bLRs made more active than inactive nose pokes, and more active nose pokes than control groups that received pseudorandom presentations of the CS and the US (Fig. 1f-g; detailed statistics in Supplementary Information).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The CS evoked dopamine release in both sign- and goal-tracking rats, but this signal increased to a greater degree in sign-trackers, which attributed incentive salience to the CS.

    “Second, the CS evoked dopamine release in both sign- and goal-tracking rats, but this signal increased to a greater degree in sign-trackers, which attributed incentive salience to the CS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Similar to surgically naïve animals, bHRs learned a sign-tracking CR and bLRs a goal-tracking CR during neurochemical data collection.

    “Similar to surgically naïve animals, bHRs learned a sign-tracking CR (session effect on lever contacts: F(5,20) = 5.76, P = 0.002) and bLRs a goal-tracking CR (session effect on food-receptacle contacts: F(5,20) = 5.18, P = 0.003) during neurochemical data collection (Fig. S2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The effect of flupenthixol on performance was also observed after the rats had already acquired their respective CR, but this finding needs to be interpreted cautiously because of a non-specific effect on activity.

    “It was also observed after the rats had already acquired their respective CR (Fig. S6), but this latter finding needs to be interpreted cautiously because of a non-specific effect on activity (Figure S6e).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Outbred rats with similar baseline locomotor activity and similar baseline levels of reward-related dopamine release in the nucleus accumbens differ in whether they are prone to learn a sign-tracking or goal-tracking CR, but they still develop patterns of dopamine release specific to that CR.

    “Outbred rats with similar baseline locomotor activity13 and similar baseline levels of reward-related dopamine release in the nucleus accumbens (see Fig. 3), differ in whether they are prone to learn a sign-tracking or goal-tracking CR, but they still develop patterns of dopamine release specific to that CR.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Boakes, R. in Operant-Pavlovian Interactions (eds Davis, H. & Hurwitz, H. M. B.) 67–97 (Erlbaum, 1977)

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Learning a goal-tracking CR does not require intact dopamine transmission, whereas learning a sign-tracking CR does.

    “Thus, learning a goal-tracking CR does not require intact dopamine transmission, whereas learning a sign-tracking CR does.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: It has been difficult to determine whether dopamine mediates the predictive or the motivational properties of reward-associated cues, because these two features are often acquired together.

  • May combine two claims.

    Interpretationown data

    The lever-CS was equally predictive, evoking a CR in both groups, but it acquired two properties of an incentive stimulus to a greater degree in bHRs than bLRs: it was more attractive, as indicated by approach behavior, and more desirable, as indicated by the ability to serve as a conditioned reinforcer.

    “In summary, the lever-CS was equally predictive, evoking a CR in both groups, but it acquired two properties of an incentive stimulus to a greater degree in bHRs than bLRs: it was more attractive, as indicated by approach behavior (Fig. 1a) and more desirable, as indicated by the ability to serve as a conditioned reinforcer (Fig. 1f).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Phasic neurotransmission in the mesolimbic dopamine system is initially triggered by the receipt of reward (US), but shifts to a cue predictive of reward (CS) after associative learning.

    “Phasic neurotransmission in the mesolimbic dopamine system is initially triggered by the receipt of reward (unconditional stimulus; US), but shifts to a cue predictive of reward (conditional stimulus; CS) after associative learning3,4.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Day, J. J., Roitman, M. F., Wightman, R. M. & Carelli, R. M. Associative learning mediates dynamic shifts in dopamine signaling in the nucleus accumbens. Nature Neurosci. 10, 1020–1028 (2007) source

      Not checked in the free run.

    • cites [4] Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599 (1997) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Only in sign-trackers is the CS an attractive incentive stimulus, and only in sign-trackers is it strongly desired (i.e. 'wanted'), in the sense that animals will work avidly to get it.

    “However, only in sign-trackers is the CS an attractive incentive stimulus, and only in sign-trackers is it strongly desired (i.e. “wanted”), in the sense that animals will work avidly to get it13.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Boakes, R. in Operant-Pavlovian Interactions (eds Davis, H. & Hurwitz, H. M. B.) 67–97 (Erlbaum, 1977)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These behavioral phenotypes are accompanied by baseline differences in dopamine transmission, with bHRs showing elevated sensitivity to dopamine agonists, increased proportion of striatal D2 receptors in a high-affinity state, greater frequency of spontaneous dopamine transients, and higher reward-related dopamine release prior to conditioning.

    “These behavioral phenotypes are accompanied by baseline differences in dopamine transmission, with bHRs showing elevated sensitivity to dopamine agonists, increased proportion of striatal D2receptors in a high-affinity state, greater frequency of spontaneous dopamine transients15, and higher reward-related dopamine release prior to conditioning, all of which could enhance their attribution of in”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [15] Stead, J. D. et al. Selective breeding for divergence in novelty-seeking traits: heritability and enrichment in spontaneous anxiety-related behaviors. Behav. Genet. 36, 697–712 (2006) source

      Not checked in the free run.

    • cites [29] Wyvell, C. L. & Berridge, K. C. Intra-accumbens amphetamine increases the conditioned incentive salience of sucrose reward: enhancement of reward "wanting" without enhanced "liking" or response reinforcement. J. Neurosci. 20, 8122–8130 (2000) source

      Not checked in the free run.

    • cites [30] Wyvell, C. L. & Berridge, K. C. Incentive sensitization by previous amphetamine exposure: increased cue-triggered "wanting" for sucrose reward. J. Neurosci. 21, 7831–7840 (2001) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    While dopamine may be necessary for the performance of both sign-tracking and goal-tracking CRs, it is only necessary for acquisition of a sign-tracking CR, indicating that these forms of learning are mediated by distinct neural systems.

    “Thus, while dopamine may be necessary for the performance of both sign-tracking and goal-tracking CRs, it is only necessary for acquisition of a sign-tracking CR, indicating that these forms of learning are mediated by distinct neural systems.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The selectively-bred rats used in this study have distinctive behavioral phenotypes, including greater behavioral disinhibition and reduced impulse control in bHRs.

    “The selectively-bred rats used in this study have distinctive behavioral phenotypes, including greater behavioral disinhibition and reduced impulse control in bHRs15.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Stead, J. D. et al. Selective breeding for divergence in novelty-seeking traits: heritability and enrichment in spontaneous anxiety-related behaviors. Behav. Genet. 36, 697–712 (2006) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    When examined off flupenthixol during the 8th test session, bHRs still failed to demonstrate a sign-tracking CR, indicating that dopamine is necessary for both the performance and the learning of a sign-tracking CR.

    “More importantly, when examined off flupenthixol during the 8th test session, bHRs still failed to demonstrate a sign-tracking CR (P≤0.01 vs. saline, session 8; Fig. 4a-c), indicating that dopamine is necessary for both the performance and the learning of a sign-tracking CR, consistent with previous findings20.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Dalley, J. W. et al. Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens. Proc. Natl Acad. Sci. USA 102, 6189–6194 (2005) source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The core of the nucleus accumbens is an important anatomical substrate for motivated behavior and has been specifically implicated as a site where dopamine acts to mediate the acquisition and/or performance of Pavlovian conditioned approach behavior.

    “The core of the nucleus accumbens is an important anatomical substrate for motivated behavior17,18 and has been specifically implicated as a site where dopamine acts to mediate the acquisition and/or performance of Pavlovian conditioned approach behavior19–22.”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [17] Berridge, K. C. in Psychology of Learning and Motivation (ed. Medin, D. L.) 223–278 (Academic Press, 2001)

      Not checked in the free run.

    • cites [18] Cardinal, R. N., Parkinson, J. A., Hall, J. & Everitt, B. J. Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci. Biobehav. Rev. 26, 321–352 (2002) source

      Not checked in the free run.

    • cites [19] Kelley, A. E. Functional specificity of ventral striatal compartments in appetitive behaviors. Ann. NY Acad. Sci. 877, 71–90 (1999) source

      Not checked in the free run.

    • cites [20] Dalley, J. W. et al. Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens. Proc. Natl Acad. Sci. USA 102, 6189–6194 (2005) source

      Not checked in the free run.

    • cites [21] Di Ciano, P., Cardinal, R. N., Cowell, R. A., Little, S. J. & Everitt, B. J. 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 (2001) source

      Not checked in the free run.

    • cites [22] Parkinson, J. A. et al. 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 (2002) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rats selectively-bred for differences in locomotor responses to a novel environment, high responders to novelty (bHR) consistently learn a sign-tracking CR but low responders to novelty (bLR) consistently learn a goal-tracking CR.

    “In rats selectively-bred for differences in locomotor responses to a novel environment14, high responders to novelty (bHR) consistently learn a sign-tracking CR but low responders to novelty (bLR) consistently learn a goal-tracking CR15.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Robinson, T. E. & Flagel, S. B. Dissociating the predictive and incentive motivational properties of reward-related cues through the study of individual differences. Biol. Psychiat. 65, 869–873 (2009) source

      Not checked in the free run.

    • cites [15] Stead, J. D. et al. Selective breeding for divergence in novelty-seeking traits: heritability and enrichment in spontaneous anxiety-related behaviors. Behav. Genet. 36, 697–712 (2006) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The CS is an effective predictor in animals that learn either a sign-tracking or a goal-tracking response; it acts as an 'excitor', evoking a CR in both.

    “The CS is an effective predictor in animals that learn either a sign-tracking or a goal-tracking response; it acts as an “excitor”, evoking a CR in both.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Another feature of an incentive stimulus is to be 'wanted' and as such animals should work to obtain it.

    “Another feature of an incentive stimulus is to be “wanted” and as such animals should work to obtain it10,16.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Berridge, K. C., Robinson, T. E. & Aldridge, J. W. Dissecting components of reward: 'liking', 'wanting', and learning. Curr. Opin. Pharmacol. 9, 65–73 (2009) source

      Not checked in the free run.

    • cites [16] Flagel, S. B. et al. An animal model of genetic vulnerability to behavioral disinhibition and responsiveness to reward-related cues: implications for addiction. Neuropsychopharmacology 35, 388–400 (2010) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Collectively, these data provide several lines of evidence demonstrating that dopamine does not act as a universal teaching signal in reward learning, but selectively participates in a form of stimulus-reward learning whereby Pavlovian incentive value is attributed to a CS.

    “Collectively, these data provide several lines of evidence demonstrating that dopamine does not act as a universal teaching signal in reward learning, but selectively participates in a form of stimulus-reward learning whereby Pavlovian incentive value is attributed to a CS.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: It has been difficult to determine whether dopamine mediates the predictive or the motivational properties of reward-associated cues, because these two features are often acquired together.

  • Classified as probably not a substantial claim.

    Premisecitation

    Human motivated behavior is subject to a wide span of individual differences ranging from highly deliberative to highly impulsive actions directed towards the acquisition of rewards.

    “Human motivated behavior is subject to a wide span of individual differences ranging from highly deliberative to highly impulsive actions directed towards the acquisition of rewards32.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Kuo, W. J., Sjostrom, T., Chen, Y. P., Wang, Y. H. & Huang, C. Y. Intuition and deliberation: two systems for strategizing in the brain. Science 324, 519–522 (2009) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The current work demonstrates that dopamine-encoded prediction-error signals are indeed present in the nucleus accumbens of sign-trackers, but not in the accumbens of goal-trackers.

    “The current work demonstrates that dopamine-encoded prediction-error signals are indeed present in the nucleus accumbens of sign-trackers, but not in the accumbens of goal-trackers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Dopamine is an integral part of reward learning that is specifically associated with the attribution of incentive salience to reward cues.

    “In sum, we show that dopamine is an integral part of reward learning that is specifically associated with the attribution of incentive salience to reward cues.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: It has been difficult to determine whether dopamine mediates the predictive or the motivational properties of reward-associated cues, because these two features are often acquired together.

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous research using site-specific dopamine antagonism and dopamine-specific lesions indicated that dopamine acts in the nucleus accumbens core to support the learning and performance of sign-tracking behavior.

    “Previous research using site-specific dopamine antagonism20 and dopamine-specific lesions21 indicated that dopamine acts in the nucleus accumbens core to support the learning and performance of sign-tracking behavior.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] Dalley, J. W. et al. Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens. Proc. Natl Acad. Sci. USA 102, 6189–6194 (2005) source

      Not checked in the free run.

    • cites [21] Di Ciano, P., Cardinal, R. N., Cowell, R. A., Little, S. J. & Everitt, B. J. 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 (2001) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Although these neurochemical data alone do not rule out the possibility that prediction-error signals are present in other dopamine terminal regions, the results from systemic dopamine antagonism demonstrate that intact dopamine transmission is generally not required for learning of a goal-tracking CR.

    “Although these neurochemical data alone do not rule out the possibility that prediction-error signals are present in other dopamine terminal regions, the results from systemic dopamine antagonism demonstrate that intact dopamine transmission is generally not required for learning of a goal-tracking CR.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Individuals who attribute reward cues with incentive salience find it more difficult to resist such cues, a feature associated with reduced impulse control.

    “Individuals who attribute reward cues with incentive salience find it more difficult to resist such cues, a feature associated with reduced impulse control15,31.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Stead, J. D. et al. Selective breeding for divergence in novelty-seeking traits: heritability and enrichment in spontaneous anxiety-related behaviors. Behav. Genet. 36, 697–712 (2006) source

      Not checked in the free run.

    • cites [31] Tomie, A., Aguado, A. S., Pohorecky, L. A. & Benjamin, D. Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping. Psychopharmacology 139, 376–382 (1998) source

      Not checked in the free run.

35 of 35

  • The paper relies on this without support.

    It has been difficult to determine whether dopamine mediates the predictive or the motivational properties of reward-associated cues, because these two features are often acquired together.

    “To date, it has been difficult to determine whether dopamine mediates the predictive or the motivational properties of reward-associated cues, because these two features are often acquired together.”

  • The paper relies on this without support.

    The neural mechanisms underlying sign-tracking and goal-tracking behavior remain to be elucidated.

    “The neural mechanisms underlying sign-tracking and goal-tracking behavior remain to be elucidated.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Attentional influences from attention for liking are difficult to overcome and may underlie maladaptive reactions in psychiatric disorders, such as enhanced susceptibility of addicted patients to drug-related cues.

    “These attentional influences are difficult to overcome and may underlie maladaptive reactions in psychiatric disorders, such as the enhanced susceptibility of addicted patients to drug-related cues (Flagel et al., 2011).”

    From Attention, learning, and the value of information (2012) · cites this paper as Flagel et al., 2011

  • Attention for liking is a powerful mechanism that automatically draws resources to stimuli with intrinsic emotional or conditioned associations.

    “Although not guided by reliability or expected information, this form of attention is a powerful mechanism, which automatically draws resources to stimuli that have intrinsic emotional or conditioned associations (Damaraju et al., 2009; Flagel et al., 2011; Hickey et al., 2010a, b; Hogarth et al., 2010; Libera and Chelazzi, 2009; Vuilleumier, 2005).”

    From Attention, learning, and the value of information (2012) · cites this paper as Flagel et al., 2011

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: F(5,40) = 0.48, p = .72

    Minor

    The paper reports p = .72 here; recomputing from the test statistic and its degrees of freedom gives p = .789. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .72 · recomputed p = .789

1 of 1

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(5, 40) = 0.48reported p = .72 · recomputed p = .789

    “F(5,40) = 0.48, p = .72”

  • ConsistentF(1, 236) = 3.02reported p = .08 · recomputed p = .084

    “F(1,236)=3.02, p = .08”

  • ConsistentF(1, 236) = 0.93reported p = .34 · recomputed p = .336

    “F(1,236)=0.93, p = .34”

  • ConsistentF(1, 33) = 4.82reported p = .04 · recomputed p = .035

    “F(1,33)=4.82, p = .04”

  • ConsistentF(5, 20) = 5.76reported p = .002 · recomputed p = .002

    “F(5,20) = 5.76, p = .002”

  • ConsistentF(5, 20) = 5.18reported p = .003 · recomputed p = .003

    “F(5,20) = 5.18, p = .003”

  • ConsistentF(5, 40) = 10.5reported p < .0001 · recomputed p < .001

    “F(5,40) = 10.5, p < .0001”

  • ConsistentF(1, 8) = 0.13reported p = .73 · recomputed p = .728

    “F(1,8) = 0.13, p = .73”

  • ConsistentF(5, 40) = 1.16reported p = .35 · recomputed p = .346

    “F(5,40) = 1.16, p = .35”

  • ConsistentF(5, 35) = 4.58reported p = .003 · recomputed p = .003

    “F(5,35) = 4.58, p = .003”

  • ConsistentF(5, 35) = 0.94reported p = .46 · recomputed p = .467

    “F(5,35) = 0.94, p = .46”

  • ConsistentF(5, 40) = 6.09reported p = .0003 · recomputed p < .001

    “F(5,40) = 6.09, p = .0003”

  • ConsistentF(5, 40) = 5.47reported p = .0006 · recomputed p < .001

    “F(5,40) = 5.47, p = .0006”

  • ConsistentF(5, 40) = 0.28reported p = .92 · recomputed p = .921

    “F(5,40) = 0.28, p = .92”

  • ConsistentF(5, 50) = 4.43reported p = .002 · recomputed p = .002

    “F(5,50) = 4.43, p = .002”

15 of 15

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

Cites

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Cited by

Sorted by citations

Related

Authors
Flagel, S. B., Clark, J. J., Robinson, T. E., Mayo, L., Czuj, A., Willuhn, I., Akers, C. A., Clinton, S. M., Phillips, P. E. M., & Akil, H.
Affiliations
  • University of Michigan (US)
  • University of Washington (US)
Corresponding author
  • Phillips, Paul E. M.
  • Akil, Huda
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2010-12-08
Volume
469
Issue
7328
Pages
53-57
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature09588
PMC
PMC3058375
OpenAlex
W2116049552
Semantic Scholar
38476c39379a177d3b95fa22125a1a7f09116670
Cited by
1,026
References
41
Citations by year
2026: 43 · 2025: 45 · 2024: 56 · 2023: 54 · 2022: 63 · 2021: 57 · 2020: 101 · 2019: 60 · 2018: 55 · 2017: 58 · 2016: 84 · 2015: 82 · 2014: 80 · 2013: 85 · 2012: 59
FWCI
24.20
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health (2t32da007278-31)
  • National Institute of Mental Health (R00MH085859, R01MH079292)
  • National Institute on Drug Abuse (F32-DA24540, P01DA021633, T32-DA07278, T32-DA007278, F32DA024540, R37DA004294, R37 DA04294, R01DA027858)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
dopamine, incentive salience, classical conditioning, incentive motivation, food cues, selective breeding, dopamine receptor blockade, cyclic voltammetry, individual differences, impulse control disorders, drug addiction
MeSH terms
Animals, Conditioning, Classical, Cues, Dopamine, Flupenthixol, Food, Disruptive, Impulse Control, and Conduct Disorders, Learning, Male, Microelectrodes, Models, Neurological, Motivation, Synaptic Transmission, Nucleus Accumbens, Phenotype, Probability, Reward, Signal Transduction, Rats, Sprague-Dawley, Dopamine Antagonists, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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