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Cited by 21Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD

Open access
Natsheh, Joman Y., Shiflett, Michael W.·2015·Frontiers in Behavioral Neuroscience
DOI 10.3389/fnbeh.2015.00326PMC PMC4659329
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Abstract

Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD) have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR; ADHD rat model) and Wistar-Kyoto rats (WKY), the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate (MPH), a commonly used ADHD medication, on goal-directed behavior, we injected rats with either MPH or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, MPH administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively.

AI snapshot

Written from the paper’s full text.

TL;DR

In adult SHR rats, a model of ADHD, goal-directed action control was impaired relative to WKY controls, but acute methylphenidate restored goal-directed responding in SHR while disrupting it in WKY rats. The authors conclude that ADHD-like behavior may involve a shift toward habitual control that MPH can partially remediate.

Key findings

  • SHR rats acquired instrumental responding and responded at greater rates than WKY rats across training; repeated-measures ANOVA showed significant effects of training block [F(3,81)=259.3, p<0.001], strain [F(1,27)=6.7, p=0.015], and block×strain interaction [F(3,81)=3.2, p=0.028], with SHR higher on blocks 2 and 4 (p=0.001 and p=0.026).
  • In the outcome devaluation test, saline-treated WKY rats showed goal-directed behavior by responding more on the valued lever [t(16)=2.6, p=0.02], whereas MPH disrupted this in WKY [t(16)=0.24, p=0.82]; SHR showed no goal-directed behavior after saline [t(11)=0.2, p=0.84], but MPH restored it [t(11)=4.65, p=0.001].
  • In the contingency degradation test, WKY responded more on the non-degraded than degraded lever [t(16)=3.98, p=0.001], while SHR showed no difference [t(10)=0.98, p=0.35]; ANOVA showed a main effect of degradation [F(1,26)=11.53, p=0.002] and degradation×strain interaction [F(1,26)=5.12, p=0.03].
  • MPH suppressed overall response rates during the devaluation test [injection effect F(1,27)=4.3, p<0.05], and SHR consumed more food than WKY before satiety [t(22)=3.69, p<0.001]; MPH reduced food consumption in WKY [t(11)=2.97, p=0.013] but not SHR [t(11)=0.923, p=0.38].

Methods

  • Twenty-nine male adult rats (P75–P105) were used: 12 SHR and 17 WKY. Rats underwent instrumental conditioning with two levers associated with grain or chocolate pellets, trained over 10 days on continuous reinforcement then VR-5, VR-15, and VR-20 schedules.
  • Goal-directed control was assessed with outcome devaluation via specific satiety to chocolate pellets followed by a 10-min extinction choice test, and with contingency degradation followed by a choice extinction test. MPH (2 mg/kg i.p.) or saline was injected before devaluation choice tests in a crossover design.
  • Data were normalized as percentage of total responses, analyzed with repeated-measures ANOVA and planned paired/independent t-tests in SPSS v20; alpha was 0.05. Locomotor activity was also measured after saline and MPH.

Limitations

  • The paper states that all rats received the same MPH dose, while therapeutic doses vary, limiting conclusions; a future dose-response study is required.
  • Evident from the text: sample sizes were small, only male rats were tested, and the study used one ADHD model (SHR) without direct neural measures.
  • Evident from the text: one SHR rat was lost from contingency degradation due to technical error (N=11), and locomotor/food-consumption tests included 12 WKY rats, which may limit some comparisons.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fnbeh.2015.00326

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

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

Claims the paper makes

8 of 45 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured

  • Interpretationcitation

    The increase in dopaminergic and noradrenergic availability in the PFC of SHR rats might be critical in restoring goal-directed actions by enhancing attentional mechanisms necessary for carrying out goal-directed behavior.

    “Thus, the increase in dopaminergic and noradrenergic availability in the PFC of SHR rats might be critical in restoring goal-directed actions by enhancing attentional mechanisms necessary for carrying out goal-directed behavior (Ostlund and Balleine, 2005; Ostlund et al., 2009).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Ostlund and Balleine, 2005 source

      The Introduction links the medial prefrontal cortex to goal-directed action in rats, and the Discussion describes its role in learning action–outcome relationships. The paper does not address SHR rats, increased dopamine or noradrenaline availability, or restoration of goal-directed behavior through enhanced attention. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Ostlund et al., 2009 source

      The Discussion reports that the dorsomedial PFC helps rats use action-sequence representations in a goal-directed manner. It does not address SHR rats, increased dopamine or noradrenaline availability, or an attentional mechanism for restoring goal-directed actions. The paper also limits the dmPFC’s role to action chunking rather than goal-directed action selection generally. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The findings of SHR operant and motor hyperactivity replicate previous research evaluating the use of the SHR strain as a model of ADHD.

    “These findings of SHR operant and motor hyperactivity replicate previous research evaluating the use of the SHR strain as a model of ADHD (Wultz et al., 1990; Hill et al., 2012).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Wultz et al., 1990 source
    • cites Hill et al., 2012 source

      The Discussion reports that SHR operant hyperactivity replicated prior findings in adult rats, and the Conclusions say the results support using SHR as an ADHD model. The paper does not establish motor hyperactivity as a separate replicated finding: the Discussion treats elevated motoric capacity as a possible contributor that cannot be ruled out, while the Background says evidence for spontaneous hyperactivity is mixed. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    NE strengthens network connectivity of the PFC and maintains persistent firing of PFC neurons during working memory tasks through stimulation of postsynaptic α2-adrenoceptors.

    “Further, recent physiological studies have shown that NE strengthens network connectivity of the PFC and maintains persistent firing of PFC neurons during working memory tasks through stimulation of postsynaptic α2-adrenoceptors (Arnsten and Dudley, 2005).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Arnsten and Dudley, 2005 source

      The Background (page unavailable) says NE improves working memory through postsynaptic α2A adrenoceptors in the PFC. The Discussion (page unavailable) reports that blocking α2 receptors reduces delay-related PFC neuronal activity, supporting the point about persistent activity during working memory. Our copy does not say that NE strengthens PFC network connectivity. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    Increasing DA signaling in the PFC enhances goal-directed behavior.

    “Increasing DA signaling in the PFC enhances goal-directed behavior (Hitchcott et al., 2007).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Hitchcott et al., 2007 source

      The Discussion says increased dopamine transmission in the ventral PFC promotes goal-directed behavior, and reports that dopamine infusions there restored sensitivity to outcome value in rats. The claim broadens this finding to the PFC generally; the paper does not report the same effect for dorsal PFC dopamine. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Findingown data

    MPH administration disrupts goal-directed behavior in WKY rats.

    “In contrast, while goal-directed behavior is well displayed in WKY rats, MPH administration disrupts this behavior.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 10
  • May combine two claims. 22

  • Classified as probably not a substantial claim.

    Premisecitation

    Lesions of the medial prefrontal cortex result in behavior that is insensitive to changes in outcome value with stimulus-elicited, rather than goal-anticipated, instrumental responding.

    “Likewise, lesions of the medial prefrontal cortex result in behavior that is insensitive to changes in outcome value with a stimulus-elicited, rather than goal-anticipated, instrumental responding (Hitchcott et al., 2007).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Hitchcott et al., 2007 source

  • May combine two claims.

    Premisecitation

    Excessive DA stimulation might cause PFC dysfunction leading to impaired inhibition of undesirable behavior and a deficit in sustaining attention.

    “However, excessive DA stimulation might cause PFC dysfunction leading to impaired inhibition of undesirable behavior, and a deficit in sustaining attention, as these two behaviors are highly regulated by dopaminergic release in the PFC (Russell, 2003; Brennan and Arnsten, 2008; Arnsten, 2011).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Russell, 2003 source
    • cites Brennan and Arnsten, 2008 source
    • cites Arnsten, 2011 source

  • May combine two claims.

    Findingown data

    There was no significant strain effect or Injection × Strain interaction on overall response rates during the devaluation test.

    “but no strain effect [F(1,27) = 3.67, p = 0.07], or Injection ∗ Strain interaction [F(1,27) = 0.002, p > 0.05].”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    MPH significantly reduced food consumption in WKY rats but not SHR rats in the 30 min after injection.

    “MPH significantly reduced food consumption in WKY rats [paired-sample t-test: t(11) = 2.97, p = 0.013] but not SHR rats [paired-sample t-test, t(11) = 0.923, p = 0.38].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    During the outcome devaluation choice test after saline injection, SHR rats responded equally on valued and devalued levers, showing no goal-directed behavior.

    “In contrast, SHR showed no goal-directed behavior, responding equally on both levers.”
    • Also stated in: § Outcome Devaluation Test · plain
      “Following saline injections, SHR rats showed no goal-directed behavior, responding equally on the valuated and devaluated levers [paired-sample t-test: t(11) = 0.2, p = 0.84]”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MPH administration prior to the outcome devaluation choice test disrupted goal-directed behavior in WKY rats, as their responses did not differ between valued and devalued levers.

    “and disrupted this behavior in WKY rats.”
    • Also stated in: § Outcome Devaluation Test · plain
      “In contrast, MPH disrupted goal-directed behavior in these rats, as their responses did not differ significantly between valuated and devaluated levers following MPH injection [paired-samples t-test: t(16) = 0.24, p = 0.82].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Many pellets remained after the 1-h session, by which time all animals had significantly curtailed food consumption.

    “Nevertheless, many pellets remained after the 1-h session, by which time all animals had significantly curtailed food consumption, suggesting that all animals had reached a state of satiety.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    SHR rats demonstrated a marked deficit in sensitivity to changes in outcome value and to changes in the action-outcome contingency.

    “While WKY rats showed goal-directed action control in both paradigms, SHR rats demonstrated a marked deficit in sensitivity to changes in outcome value and to changes in the action–outcome contingency.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MPH administration prior to the outcome devaluation choice test restored goal-directed behavior in SHR rats, as shown by greater responding on the valued lever than the devalued lever.

    “However, MPH administration prior to the choice test restored goal-directed behavior in SHR”
    • Also stated in: § Outcome Devaluation Test · boosted
      “MPH restored goal-directed behavior in these rats, as shown by significantly greater responding on the valuated lever compared to the devaluated lever after MPH injection [paired-sample t-test: t(11) = 4.65, p = 0.001].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was a significant main effect of degradation and Degradation × Strain interaction in the contingency degradation test.

    “A repeated-measures ANOVA revealed a significant main effect of degradation [F(1,26) = 11.53, p = 0.002] and Degradation ∗ Strain interaction [F(1,26) = 5.12, p = 0.03].”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    MPH and saline injections were intermixed for all experiments; therefore, there was no injection-order effect to influence outcome devaluation responding.

    “MPH and saline injections were intermixed for all experiments; therefore, there was no injection-order effect to influence outcome devaluation responding.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The normality of data distribution was checked using Kolmogorov-Smirnov tests, and all data were normally distributed (p > 0.1).

    “The normality of data distribution was checked using Kolmogorov–Smirnov tests. All data were normally distributed (p > 0.1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    SHR rats show deficits in sustained attention, motor impulsiveness, and hyperactivity in a novel environment.

    “SHR rats show deficits in sustained attention, motor impulsiveness, and hyperactivity in a novel environment (Knardahl and Sagvolden, 1979; Sagvolden et al., 1992, 2005b; Wultz and Sagvolden, 1992; Sagvolden, 2000).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Knardahl and Sagvolden, 1979 source
    • cites Sagvolden et al., 1992, 2005b

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Wultz and Sagvolden, 1992 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Lesions of the dorsolateral striatum brought normal habitual actions under the control of the goal-directed system.

    “Further, they have shown that lesions of the dorsolateral striatum brought normal habitual actions under the control of the goal-directed system.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Yin et al., 2004 source

  • May combine two claims.

    Interpretationown data

    SHR rats' impaired goal-directed behavior is not due to a lack of knowledge of causal consequences or to a failure of the devaluation process prior to the extinction test.

    “Overall, our data suggest that SHR rats’ impaired goal-directed behavior is not due to a lack of knowledge of causal consequences or to a failure of the devaluation process prior to the extinction test.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    All rats were injected with the same dose of MPH, which limits the conclusions that can be drawn from the study.

    “Finally, one limitation of our study was injecting all rats with the same dose of MPH, while many studies have reported significant variations in the therapeutic doses of MPH. The use of one drug dose limits the conclusions we can draw from this study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Data were normalized by dividing responses on the valued or devalued lever by total responses because of strain differences in overall response rates during the tests.

    “Data were normalized by dividing responses on the valued or devalued lever by total (valued plus devalued) responses. Normalization was carried out because of strain differences in overall response rates during the tests.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    MPH corrects attentional and motor impairments in SHR rats.

    “Likewise, MPH corrects attentional and motor impairments in SHR rats, lending further support for SHR rats as a model of human ADHD (Sagvolden et al., 2005a,b; Kantak et al., 2008).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Sagvolden et al., 2005a,b source
    • cites Kantak et al., 2008 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Contemporary theories of action control suggest that two processes guide action selection: a goal-directed system based on current knowledge of action-outcome contingencies and a habit system based on acquired stimulus-response associations.

    “Contemporary theories of action control suggest that two processes guide action selection: (1) a goal-directed system based on current knowledge of action–outcome contingencies and (2) a habit system based on acquired stimulus–response associations (Dickinson, 1985).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dickinson, 1985 source

  • May combine two claims.

    Premisecitation

    SHR rats display reduced DA signaling and increased DAT expression, similar to ADHD patients.

    “Further, SHR rats display reduced DA signaling and increased DA transporter (DAT) expression, similar to ADHD patients (Russell et al., 1995; Russell, 2003; Heal et al., 2008; Roessner et al., 2010).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Russell et al., 1995 source
    • cites Russell, 2003 source
    • cites Heal et al., 2008 source

  • May combine two claims.

    Interpretationreasoning

    The insensitivity to outcome devaluation in SHR rats might suggest that the neural circuits required for goal-directed actions are dysfunctional in these animals and thus they rely on the habit system instead to control responding.

    “Accordingly, the insensitivity to outcome devaluation in SHR rats might suggest that the neural circuits required for goal-directed actions are dysfunctional in these animals and thus they rely on the habit system instead to control responding.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Changes in operant behavior in response to changes in either outcome value or the action-outcome contingency reflect goal-directed action control, whereas lack of sensitivity to these changes likely reflects habitual action control.

    “For example, changes in operant behavior in response to changes in either outcome value or the action–outcome contingency reflect goal-directed action control, whereas lack of sensitivity to these changes likely reflects habitual action control.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dickinson, 1985 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Neural activity in the PFC is related to engagement of specific action-outcome associations.

    “Electrophysiological studies using primates (Matsumoto et al., 2003; Matsumoto and Tanaka, 2004) and rats (Mulder et al., 2003) have found neural activity in the PFC related to engagement of specific action–outcome associations.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Matsumoto et al., 2003 source
    • cites Matsumoto and Tanaka, 2004 source
    • cites Mulder et al., 2003 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    For the contingency degradation test, data for one SHR rat were lost due to a technical error.

    “For the contingency degradation test, we lost data for one SHR rat due to a technical error.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively.

    “This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Goal-directed/habitual action control in SHR rats had not been assessed using operant outcome devaluation/contingency degradation paradigms before this study.

  • May combine two claims.

    Premisecitation

    The therapeutic dose of MPH works primarily via increasing DA signaling through DAT blockade in the PFC and enhancing extracellular DA release in the striatum, and indirectly increasing NE actions through blockade of its transporters.

    “The therapeutic dose of MPH works primarily via (1) increasing DA signaling through multiple actions, including DAT blockade in the PFC, and significantly enhancing extracellular DA release in the striatum (Volkow et al., 2002; Wilens, 2008) and (2) indirectly increasing NE actions through blockade of its transporters (Berridge et al., 2006).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Volkow et al., 2002 source
    • cites Wilens, 2008 source
    • cites Berridge et al., 2006 source

  • May combine two claims.

    Premisecitation

    Cortico-striatal circuits that include the PFC and striatum mediate goal-directed behavior and habitual learning.

    “Cortico-striatal circuits that include the PFC and striatum mediate goal-directed behavior and habitual learning.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Matsumoto et al., 2003 source
    • cites Yin et al., 2005 source
    • cites Yin et al., 2004 source

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

    Study design and conductown data

    Since results showed no preference for chocolate or grain pellets, only one outcome was devalued to control for this variable across medication status.

    “Since our results showed that rats had no preference for chocolate or grain pellets (see Results section: “Instrumental Training”), we only devalued one of the two outcomes to control for this variable across medication status (MPH and saline injections).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Administration of MPH restored goal-directed behavior by increasing the magnitude of the anticipatory DA cell firing to predictive cues.

    “In the context of DA transfer deficit theory of ADHD, one can argue that administration of MPH restored goal-directed behavior by increasing the magnitude of the anticipatory DA cell firing to predictive cues (pressing the lever) (Tripp and Wickens, 2009, 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tripp and Wickens, 2009, 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

29 of 29

  • The paper relies on this without support.

    Goal-directed/habitual action control in SHR rats had not been assessed using operant outcome devaluation/contingency degradation paradigms before this study.

    “Behavior of SHR rats has yet to be assessed using these paradigms.”
    “Although previous research has shown overactive instrumental responding in SHR rats that was corrected by MPH, it is not known whether animals performed responses in a goal-directed or habitual manner (Sagvolden et al., 1993).”

  • The paper relies on this without support.

    The loss of data from one SHR rat in the contingency degradation test did not bias the group results.

    “For the contingency degradation test, we lost data for one SHR rat due to a technical error.”

  • The paper relies on this without support.

    The dose of MPH used in this study corresponds to a therapeutic dose in humans.

    “The therapeutic dose of MPH works primarily via (1) increasing DA signaling through multiple actions, including DAT blockade in the PFC, and significantly enhancing extracellular DA release in the striatum (Volkow et al., 2002; Wilens, 2008) and (2) indirectly increasing NE actions through blockade of its transporters (Berridge et al., 2006).”
    “Finally, one limitation of our study was injecting all rats with the same dose of MPH, while many studies have reported significant variations in the therapeutic doses of MPH.”

  • The paper relies on this without support.

    Findings in SHR rats can be generalized to ADHD patients.

    “These results suggest that clinical symptoms exhibited by ADHD patients may reflect impaired goal-directed action control and that MPH may activate this system to re-establish goal-directed behavior.”
    “We show for the first time that goal-directed behavior is impaired in a rat model of ADHD and can be remediated in SHR rats with MPH treatment.”

  • The paper relies on this without support.

    WKY rats are an appropriate normotensive control for SHR rats.

    “In this study, we show using outcome devaluation and contingency degradation paradigms that SHR rats have a deficit in goal-directed behavior compared to normotensive WKY rats.”
    “Both control WKY rats and SHR rats were successful at acquiring an instrumental response, with SHR rats showing a significantly greater response rate during training.”
5 of 5

Statistics that don’t add up

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

  • Inconsistent p-value: F(1,22) = 25.52, p = .018

    Minor

    The paper reports p = .018 here; recomputing from the test statistic and its degrees of freedom gives p < .001. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .018 · recomputed p < .001

  • p-value fits an unstated one-tailed test: t(22) = 3.69, p < .001

    Minor

    The paper reports p < .001 here; recomputing from the test statistic and its degrees of freedom gives p = .001 (two-tailed). The reported value is what a one-tailed test gives, but the paper does not say near this result that a one-tailed test was used.

    Reported p < .001 · recomputed p = .001

2 of 2

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 upt(22) = 3.69reported p < .001 · recomputed p = .001

    “t(22) = 3.69, p < .001”

  • Doesn’t add upF(1, 22) = 25.52reported p = .018 · recomputed p < .001

    “F(1,22) = 25.52, p = .018”

  • ConsistentF(3, 81) = 259.3reported p < .001 · recomputed p < .001

    “F(3,81) = 259.3, p < .001”

  • ConsistentF(1, 27) = 6.7reported p = .015 · recomputed p = .015

    “F(1,27) = 6.7, p = .015”

  • ConsistentF(3, 81) = 3.2reported p = .028 · recomputed p = .028

    “F(3,81) = 3.2, p = .028”

  • ConsistentF(1, 11) = 2.88reported p = .12 · recomputed p = .118

    “F(1,11) = 2.88, p = .12”

  • ConsistentF(1, 16) = 0.36reported p = .56 · recomputed p = .557

    “F(1,16) = 0.36, p = .56”

  • ConsistentF(1, 16) = 4.83reported p = .043 · recomputed p = .043

    “F(1,16) = 4.83, p = .043”

  • ConsistentF(1, 11) = 12.52reported p = .005 · recomputed p = .005

    “F(1,11) = 12.52, p = .005”

  • Consistentt(16) = 2.6reported p = .02 · recomputed p = .019

    “t(16) = 2.6, p = .02”

  • Consistentt(16) = 0.24reported p = .82 · recomputed p = .813

    “t(16) = 0.24, p = .82”

  • Consistentt(11) = 0.2reported p = .84 · recomputed p = .845

    “t(11) = 0.2, p = .84”

  • Consistentt(11) = 4.65reported p = .001 · recomputed p < .001

    “t(11) = 4.65, p = .001”

  • ConsistentF(1, 27) = 4.3reported p < .05 · recomputed p = .048

    “F(1,27) = 4.3, p < .05”

  • ConsistentF(1, 27) = 3.67reported p = .07 · recomputed p = .066

    “F(1,27) = 3.67, p = .07”

  • ConsistentF(1, 27) = 0.002reported p > .05 · recomputed p = .965

    “F(1,27) = 0.002, p > .05”

  • Consistentt(16) = 1.88reported p = .079 · recomputed p = .078

    “t(16) = 1.88, p = .079”

  • Consistentt(11) = 1.15reported p > .05 · recomputed p = .275

    “t(11) = 1.15, p > .05”

  • ConsistentF(1, 26) = 11.53reported p = .002 · recomputed p = .002

    “F(1,26) = 11.53, p = .002”

  • ConsistentF(1, 26) = 5.12reported p = .03 · recomputed p = .032

    “F(1,26) = 5.12, p = .03”

  • Consistentt(16) = 3.98reported p = .001 · recomputed p = .001

    “t(16) = 3.98, p = .001”

  • Consistentt(10) = 0.98reported p = .35 · recomputed p = .350

    “t(10) = 0.98, p = .35”

  • Consistentt(11) = 2.97reported p = .013 · recomputed p = .013

    “t(11) = 2.97, p = .013”

  • Consistentt(11) = 0.923reported p = .38 · recomputed p = .376

    “t(11) = 0.923, p = .38”

  • ConsistentF(1, 11) = 26.4reported p < .001 · recomputed p < .001

    “F(1,11) = 26.4, p < .001”

  • ConsistentF(2, 22) = 13.6reported p < .01 · recomputed p < .001

    “F(2,22) = 13.6, p < .01”

  • ConsistentF(2, 22) = 2.36reported p > .05 · recomputed p = .118

    “F(2,22) = 2.36, p > .05”

  • Consistentt(22) = 6.45reported p < .001 · recomputed p < .001

    “t(22) = 6.45, p < .001”

  • Consistentt(22) = 7.77reported p < .001 · recomputed p < .001

    “t(22) = 7.77, p < .001”

  • Consistentt(22) = 11.62reported p < .001 · recomputed p < .001

    “t(22) = 11.62, p < .001”

  • Consistentt(22) = 3.85reported p = .001 · recomputed p < .001

    “t(22) = 3.85, p = .001”

31 of 31

Self-check

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

Each contradiction between two passages listed here was confirmed by an independent check.

  • Within-strain paired locomotor tests have incorrect degrees of freedom

    Minor

    Figure 5 gives 12 rats per strain. A paired t-test within either strain therefore has 12 − 1 = 11 degrees of freedom, not 22 as reported for both tests.

    Reported 22 · recomputed 11

  • Food-consumption table gives conflicting WKY sample sizes

    Minor

    The methods state that food-consumption tests used 12 WKY rats, whereas the note to the food-consumption table says they used 17.

  • Discussion reverses the SHR contingency-degradation result

    Minor

    The discussion says SHR rats responded significantly less on the degraded lever, but the Results report no significant difference between the two levers. This reverses a result used to support the paper's conclusion about impaired goal-directed control.

3 of 3

Cites

Flagged first, then by citations

1 of the 57 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Hill, 1970, Facilitation of conditioned reinforcement as a mechanism of psychomotor stimulation, Amphetamines and Related Compounds, 781

Cited by

Sorted by citations

Related

Authors
Natsheh, J. Y., & Shiflett, M. W.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Natsheh, Joman Y.
ORCID
Venue
Frontiers in Behavioral Neuroscience
Publisher
Frontiers Media SA
Published
2015-11-25
Volume
9
Pages
326-326
ISSN
1662-5153 (ISSN-L)
DOI
10.3389/fnbeh.2015.00326
PMC
PMC4659329
OpenAlex
W2204218963
Semantic Scholar
6033a9ec6f4c10a5f4f345e0d454eefaa00bb6c0
Cited by
21
References
57
Citations by year
2025: 3 · 2024: 3 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 4 · 2016: 2
FWCI
1.62
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Drug Abuse (R15DA029544)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
methylphenidate, goal-directed behavior, attention deficit hyperactivity disorder, spontaneously hypertensive rats, Wistar-Kyoto rats, operant conditioning, choice behavior, outcome devaluation, satiety, habitual behavior, animal model of ADHD, stimulant medication effects

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 2026-11-01.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-01.

Cited sources are checked by gpt-6-sol.

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.

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