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Cited by 17Nicotinic Acetylcholine Receptors StudyPrenatal Substance Exposure EffectsSmoking Behavior and Cessation

Impaired auditory discrimination learning following perinatal nicotine exposure or β2 nicotinic acetylcholine receptor subunit deletion

Open access
Horst, Nicole K., Heath, Christopher J., Neugebauer, Nichole M., Kimchi, Eyal Y., Laubach, Mark, Picciotto, Marina R.·2012·Behavioural Brain Research
DOI 10.1016/j.bbr.2012.03.002PMC PMC3334440
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Abstract

Maternal smoking during pregnancy can impair performance of the exposed offspring in tasks that require auditory stimulus processing and perception; however, the tobacco component(s) responsible for these effects and the underlying neurobiological mechanisms remain uncertain. In this study, we show that administration of nicotine during mouse perinatal development can impair performance in an auditory discrimination paradigm when the exposed animals are mature. This suggests that nicotine disrupts auditory pathways via nicotinic acetylcholine receptors (nAChRs) that are expressed at an early stage of development. We have also determined that mice which lack nAChRs containing the β2 subunit (β2* nAChRs) exhibit similarly compromised performance in this task, suggesting that β2* nAChRs are necessary for normal auditory discrimination or that β2* nAChRs play a critical role in development of the circuitry required for task performance. In contrast, no effect of perinatal nicotine exposure or β2 subunit knockout was found on the acquisition and performance of a differential reinforcement of low rate task. This suggests that the auditory discrimination impairments are not a consequence of a general deficit in learning and memory, but may be the result of compromised auditory stimulus processing in the nicotine-exposed and knockout animals.

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Written from the paper’s full text.

TL;DR

Perinatal nicotine exposure or deletion of the β2 nicotinic acetylcholine receptor subunit impaired auditory discrimination learning in adult mice, while performance in a differential reinforcement of low rate (DRL) task was unaffected. The authors conclude the deficits likely reflect compromised auditory stimulus processing rather than a general learning/memory impairment or altered response rates.

Key findings

  • Perinatally nicotine-exposed mice had lower auditory discrimination ratios than saccharin controls in later training sessions (Session 5: 0.097±0.024 vs 0.18±0.023, LSD p=0.013; Session 6: 0.13±0.028 vs 0.23±0.026, LSD p=0.015), but performed comparably by Session 7 (0.23±0.038 vs 0.28±0.036, LSD p=0.32); final analysis included 21 nicotine-treated and 24 saccharin-treated mice.
  • β2 nAChR subunit knockout mice showed impaired discrimination overall (knockout<wild-type: 0.049±0.010 vs 0.13±0.012, LSD p=0.005) and remained impaired in later sessions (Session 6: 0.063±0.034 vs 0.30±0.040, LSD p=0.011; Session 7: 0.099±0.042 vs 0.35±0.049, LSD p=0.018); final analysis included 6 knockout and 5 wild-type mice.
  • In the DRL task, neither perinatal nicotine exposure nor β2 knockout impaired performance; mice reduced total response rate and increased rewards over 12 days (e.g., nicotine/saccharin total response rate Day 12<Day 1: 7.71±0.37<10.1±0.67, LSD p=0.006; rewards Day 12>Day 1: 5.74±0.12>5.09±0.14, LSD p=0.027).
  • β2 knockout mice had elevated false alarm responding overall (knockout>wild-type: 2.49±0.040>2.24±0.047, LSD p=0.015), and nicotine-exposed mice made more magazine entries during the intertrial interval when no stimulus was delivered (nicotine>saccharin: 1.31±0.056>1.12±0.052, LSD p=0.018).

Methods

  • C57BL/6J mice were exposed perinatally to 200 μg/ml nicotine plus 2% saccharin or pH-matched saccharin vehicle via maternal drinking water throughout pregnancy until postnatal day 21; β2 nAChR subunit knockout and wild-type siblings were backcrossed onto C57BL/6J for at least 20 generations.
  • Auditory discrimination training used operant arenas with nosepoke and magazine responses, 12 kHz vs 15 kHz tones at ~60 dBA, and a discrimination ratio = (P(Hits) − P(False Alarms)) / (P(Hits) + P(False Alarms)); mice were tested for 7 consecutive days. A subset was then trained on a DRL12 schedule.
  • Analyses used mixed factorial repeated-measures ANOVA over sessions, Huynh-Feldt correction when sphericity failed, and Fisher’s LSD pairwise comparisons; outliers with discrimination ratios outside 1.5× the interquartile range on any test day were excluded; significance was p<0.05.

Limitations

  • The paper states that the β2 knockout study had a small number of subjects, so only main effects and second-order interactions were considered, and outlier exclusion further reduced subject numbers.
  • The paper states it did not directly determine whether β2 subunit expression is required during development or adulthood for normal auditory discrimination performance.
  • Evident from the text: only male mice were used for the reported behavioral cohorts, so sex differences are not addressed; the mechanistic link to altered thalamocortical/corticothalamic circuitry is inferred rather than directly tested in this study.

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

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Registry

Crossref · 10.1016/j.bbr.2012.03.002

Cites

71 of 71 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 84 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Perinatal nicotine exposure in mice impairs performance in an auditory discrimination paradigm when the exposed animals are mature.

    “In this study, we show that administration of nicotine during mouse perinatal development can impair performance in an auditory discrimination paradigm when the exposed animals are mature.”
    • Also stated in: § 3.1. Auditory discrimination learning is altered in mice exposed to perinatal nicotine · plain
      “In summary, perinatal nicotine exposure disrupted learning of the auditory discrimination procedure, as measured by Discrimination Ratio.”
    Quote in the paperSubstantial claim
  • Findingown data

    Over sessions, mice in both saccharin and nicotine treatment groups responded more rapidly following tone delivery.

    “responded more rapidly following tone delivery (Table 1; Hit latency, Session 7<Session 1: −0.22±0.042<0.17±0.040, LSD p<0.001; False Alarm latency, Session 7<Session 1: 0.063±0.042<0.23±0.038, LSD p=0.001; Figure 2C)”
    Quote in the paperNot a substantial claim
  • Findingown data

    There were significant session by treatment interactions in both Hit and False Alarm measures.

    “There were significant session x treatment interactions in both of these measures (Table 1).”
    Quote in the paperSubstantial claim
  • Findingown data

    Mice from both saccharin and nicotine treatment groups learned to discriminate between 12 kHz and 15 kHz tones, as shown by an overall increase in Discrimination Ratio over days.

    “Mice from both groups learned to discriminate between 12 kHz and 15 kHz auditory tones, as evidenced by an overall increase in the Discrimination Ratio over days”
    Quote in the paperSubstantial claim
  • Findingown data

    There were no treatment-related differences in the speed with which mice responded to the tones.

    “There were no treatment-related differences in the speed with which mice responded to the tones (Table 1; Figure 2C).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 44
  • Classified as probably not a substantial claim. 23
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    On session 6, nicotine-treated mice had higher Hit and False Alarm responses than saccharin controls.

    “Session 6: Hit, nicotine>saccharin: 2.87±0.069<2.67±0.065, LSD p=0.041; False Alarm, nicotine>saccharin: 2.13±0.096>1.81±0.089, LSD p=0.020”
    Quote in the paperSubstantial claim

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

    Findingown data

    Mice assigned to the fixed interval schedule tended to respond more during the intertrial interval than mice assigned to the random interval schedule.

    “Mice assigned to the fixed interval schedule tended to respond more during the ITI than mice assigned to the random interval schedule (fixed (n=22) > random (n=23): 1.32±0.055>1.12±0.053, LSD p=0.012).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Perinatal nicotine exposure or β2 subunit knockout has no effect on acquisition and performance of a differential reinforcement of low rate task.

    “In contrast, no effect of perinatal nicotine exposure or β2 subunit knockout was found on the acquisition and performance of a differential reinforcement of low rate task.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In both saccharin and nicotine treatment groups, False Alarm responding decreased over training sessions.

    “This effect was driven by a reduction in False Alarm responding over days (Table 1; Session 7<Session 1: 1.81±0.079<2.62±0.039, LSD p<0.001; Figure 2B)”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In both saccharin and nicotine treatment groups, Hit responding remained stable throughout training.

    “as the rate of Hit responding remained stable throughout training (Table 1; Figure 2B)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was a strong trend toward a main effect of treatment on Discrimination Ratio and a significant treatment by session interaction.

    “There was a strong trend toward a main effect of treatment (Table 1; nicotine<saccharin: 0.087±0.014<0.13±0.013, LSD p=0.055; Figure 2A) and a significant interaction between treatment and session on the Discrimination Ratio (Table 1).”
    Quote in the paperSubstantial claim

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

    Findingown data

    There was a significant session by treatment effect on intertrial interval nosepoking, but no significant post hoc effects.

    “There was a significant session x treatment effect on ITI nosepoking (Table 1), but no significant post hoc effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was a significant main effect of treatment on the proportion of magazine responses during the intertrial interval when no stimulus was delivered; nicotine-exposed mice made more such responses than controls.

    “However, there was a significant main effect of treatment on the proportion of responses in the magazine during the ITI when no stimulus was delivered (Table 1). Mice exposed to nicotine during perinatal development made more such responses than control mice (nicotine>saccharin: 1.31±0.056>1.12±0.052, LSD p=0.018; Figure 2B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was no interaction between treatment and schedule, nor an effect of treatment on latency to respond in the magazine after an intertrial interval nosepoke entry.

    “There was no interaction between treatment and schedule, nor was there an effect of treatment on the latency to respond in the magazine after an ITI nosepoke entry (Table 1; Figure 2D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Nicotine-treated mice had lower Discrimination Ratios than saccharin controls in sessions 5 and 6, but performed comparably by session 7.

    “Nicotine-treated mice had lower Discrimination Ratios in later sessions (Session 5, nicotine<saccharin: 0.097±0.024<0.18±0.023, LSD p=0.013; Session 6, nicotine<saccharin: 0.13±0.028<0.23±0.026, LSD p=0.015; Figure 2A), but performed comparably to saccharin control mice by the seventh day of training (Session 7, nicotine=saccharin: 0.23±0.038=0.28±0.036, LSD p=0.32; Figure 2A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Response latencies for the Rewarded Tone decreased over days, while False Alarm latencies did not change and magazine responses in the absence of tone delivery slowed.

    “Response latencies for the Rewarded Tone decreased over days (Table 2; Session 7<Session 1: −0.112±0.077<0.21±0.020, LSD p=0.013; Figure 3C), while there was no change in False Alarm latencies (Table 2; Figure 3C) and slowing of magazine responses in the absence of tone delivery (Table 2; Session 7>Session 1: 1.96±0.18>0.76±0.11, LSD p=0.001; Figure 3D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was a significant session by genotype interaction, with β2 knockout mice discriminating significantly less well than wild-type controls in sessions 6 and 7.

    “There was also a significant session × genotype interaction (Table 2), with β2 knockout mice discriminating significantly less well than wild-type controls in later sessions (Session 6, knockout<wild-type: 0.063±0.034<0.30±0.040, LSD p=0.011; Session 7, knockout<wild-type: 0.099±0.042<0.35±0.049, LSD p=0.018; Figure 3A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The increase in Discrimination Ratio in both β2 knockout and wild-type genotypes was primarily due to reduction of False Alarm rate, while Hit probability remained stable.

    “The increase in Discrimination Ratio was primarily due to reduction of the False Alarm rate (Table 2; Session 7<Session 1: 1.93±0.072<2.77±0.064, LSD p=0.003; Figure 3B), as the probability of a Hit response remained stable over days (Table 2; Figure 3B).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The quicker responding to the 12 kHz tone compared to the 15 kHz tone in False Alarm latency was only significant at a trend level.

    “However, the comparatively quicker responding to the 12 kHz tone was only significant at a trend level by LSD pair-wise comparison (12 kHz (n=4) <15 kHz (n=7): 0.089±0.050<0.26±0.040, LSD p=0.057).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    There was a significant main effect of schedule on the latency to respond in the magazine after an ITI nosepoke.

    “There was also a significant main effect of schedule on the latency to respond in the magazine after an ITI nosepoke (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were session × genotype effects on ITI nosepoke rates and on the probability of responding in the magazine during the ITI.

    “There were session × genotype effects on ITI nosepoke rates and on the probability of responding in the magazine during the ITI (Table 2).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    There was a significant main effect of stimulus assignment on False Alarm latency in the auditory discrimination task.

    “In addition, there was a significant main effect of stimulus assignment on False Alarm latency (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no significant differences by pair-wise LSD for ITI nosepoke rates or magazine responding during the ITI.

    “However, there were no significant differences by pair-wise LSD (Figure 3B).”
    Quote in the paperSubstantial claim

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

    Findingown data

    There was a main effect of previous assignment to either fixed or random interval schedules on total response rate in the DRL task.

    “Interestingly, there was a main effect of previous assignment to either fixed or random interval schedules on total response rate in the DRL task (Table 4; total response rate, fixed (n=6) > random (n=5): 9.32±0.44<7.42±0.50, LSD p=0.025).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neither developmentally-treated nor β2 knockout mice displayed treatment- or genotype-dependent differences in performance in a DRL schedule.

    “By contrast, neither developmentally-treated or β2 knockout mice displayed treatment- or genotype-dependent differences in performance in a DRL schedule”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All mice learned to withhold responding during the 12 sec delay in the DRL task, as shown by a decrease in total response rate from Day 1 to Day 12.

    “All mice learned to withhold responding during the 12 sec delay (Table 4; total response rate, Day 12<Day 1: 7.66±0.32<10.3±1.10, LSD p=0.038; Figure 6A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The number of rewards earned increased over sessions in the DRL task, but the difference between rewards earned in the first vs. last session did not reach significance.

    “The number of rewards earned increased over sessions (Table 4), but the difference between rewards earned in the first vs. last session did not reach significance (rewards, Day 12>Day 1: 5.75±0.25<5.24±0.27, LSD p=0.187; Figure 6B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We found little evidence of increased magazine entries in the absence of tone delivery in the auditory discrimination task and no evidence of elevated nosepoke responding in the DRL procedure in our developmentally exposed mice.

    “However, we found little evidence of increased magazine entries in the absence of tone delivery in the auditory discrimination task and no evidence of elevated nosepoke responding in the DRL procedure in our developmentally exposed mice”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mice in the auditory discrimination task approach the reward magazine nearly 100% of the time when a Rewarded Tone is played, but much less than this when no tone is played.

    “as they approach the reward magazine nearly 100% of the time when a Rewarded Tone is played (Figures 2B, 3B: circles), but much less than this when no tone is played (Figures 2B, 3B: squares).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Auditory discrimination impairments in nicotine-exposed and β2 knockout animals are not a consequence of a general deficit in learning and memory, but may result from compromised auditory stimulus processing.

    “This suggests that the auditory discrimination impairments are not a consequence of a general deficit in learning and memory, but may be the result of compromised auditory stimulus processing in the nicotine-exposed and knockout animals.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The auditory discrimination task specifically measures auditory stimulus processing rather than other cognitive or motivational processes.
    • Rests on an assumption: The differential reinforcement of low rate task does not depend on auditory stimulus processing.

  • May combine two claims.

    Interpretationown data

    β2* nicotinic acetylcholine receptors are necessary for normal auditory discrimination or play a critical role in development of the circuitry required for task performance.

    “suggesting that β2* nAChRs are necessary for normal auditory discrimination or that β2* nAChRs play a critical role in development of the circuitry required for task performance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Non-significant differences between Hit and False Alarm measures contributed to treatment-related differences in Discrimination Ratio, with elevated False Alarm responding contributing significantly on session 6.

    “Therefore, it would appear that non-significant differences between these measures contributed to the treatment-related differences in the Discrimination Ratio, with elevated False Alarm responding contributing significantly on session 6.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Mice treated with nicotine during perinatal development were equally able to withhold responding in the nosepoke port during the intertrial interval, but once such a response was made, they were more likely to approach the reward magazine.

    “Mice treated with nicotine during perinatal development were therefore equally able to withhold responding in the nosepoke port during the ITI, but once such a response was made, they were more likely to approach the reward magazine.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Nicotine is a likely tobacco component that could disrupt neurodevelopment and induce persistent changes in sensory processing through actions at nicotinic acetylcholine receptors expressed early in central nervous system development.

    “Among the numerous components in tobacco, nicotine is a likely component that could disrupt neurodevelopment and induce these persistent changes in sensory processing through its actions at nicotinic acetylcholine receptors (nAChRs), which are expressed early in central nervous system development [19–23].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [19] Zoli M Le Novere N Hill JA Jr. Changeux JP Developmental regulation of nicotinic ACh receptor subunit mRNAs in the rat central and peripheral nervous systems J Neurosci 1995 15 1912 39 7891142 PMC6578133

      Not checked in the free run.

    • cites [20] Hellstrom-Lindahl E Gorbounova O Seiger A Mousavi M Nordberg A Regional distribution of nicotinic receptors during prenatal development of human brain and spinal cord Brain Res Dev Brain Res 1998 108 147 60 9693793

      Not checked in the free run.

    • cites [21] Dwyer JB Broide RS Leslie FM Nicotine and brain development Birth Defects Res C Embryo Today 2008 84 30 44 18383130 source

      Not checked in the free run.

    • cites [22] Dwyer JB McQuown SC Leslie FM The dynamic effects of nicotine on the developing brain Pharmacol Ther 2009 122 125 39 19268688 PMC2746456 source

      Not checked in the free run.

    • cites [23] Winzer-Serhan UH Long-term consequences of maternal smoking and developmental chronic nicotine exposure Front Biosci 2008 13 636 49 17981576

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Perinatal exposure using this dose and method has minimal impact on birth weight or early postnatal weight gain or maternal care behavior in this strain while affecting sensory processing in adulthood.

    “It has also been shown that perinatal exposure using this dose and method of administration has minimal impact on birth weight or early postnatal weight gain or on measures of maternal care behavior in this strain [42] while affecting sensory processing in adulthood [27].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [42] Heath CJ Horst NK Picciotto MR Oral nicotine consumption does not affect maternal care or early development in mice but results in modest hyperactivity in adolescence Physiol Behav 2010 101 764 9 20826170 PMC2975773

      Not checked in the free run.

    • cites [27] Heath CJ King SL Gotti C Marks MJ Picciotto MR Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through alpha4/beta2/alpha5 nicotinic acetylcholine receptors Neuropsychopharmacology 2010 35 2324 38 20736992 PMC2955839 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The 200 μg/ml nicotine dose has behavioral and biochemical efficacy in adult mice, induces neurodevelopmental alterations, and has minimal effects on pregnancy in the C57BL/6J strain.

    “The 200 μg/ml nicotine dose was selected as it has been shown previously to have both behavioral and biochemical efficacy in the adult mouse [37–40], to induce alterations in neurodevelopment [41], and to have minimal effects on pregnancy in the C57BL/6J strain [41].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [37] Brunzell D Russell D Picciotto M In vivo nicotine treatment regulates mesocorticolimbic CREB and ERK signaling in C57Bl/6J mice J Neurochem 2003 84 1431 41 12614343

      Not checked in the free run.

    • cites [38] Brunzell D Chang J Schneider B Olausson P Taylor J Picciotto M beta2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice Psychopharmacology (Berl) 2006 184 328 38 16133126

      Not checked in the free run.

    • cites [39] Caldarone B King S Picciotto M Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice Neurosci Lett 2008 439 187 91 18524488 PMC2491450

      Not checked in the free run.

    • cites [40] King S Caldarone B Picciotto M Beta2-subunit-containing nicotinic acetylcholine receptors are critical for dopamine-dependent locomotor activation following repeated nicotine administration Neuropharmacology 2004 47 Suppl 1 132 9 15464132

      Not checked in the free run.

    • cites [41] Pauly JR Sparks JA Hauser KF Pauly TH In utero nicotine exposure causes persistent, gender-dependant changes in locomotor activity and sensitivity to nicotine in C57Bl/6 mice Int J Dev Neurosci 2004 22 329 37 15380832

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The α4β2α5 nicotinic acetylcholine receptor subtype may have a role in refinement of layer VI corticothalamic terminals.

    “It has also been suggested that the α4β2α5 nAChR subtype may have a role in the refinement of the layer VI corticothalamic terminals that permit cortical feedback modulation of thalamic activity [27, 28].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] Heath CJ King SL Gotti C Marks MJ Picciotto MR Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through alpha4/beta2/alpha5 nicotinic acetylcholine receptors Neuropsychopharmacology 2010 35 2324 38 20736992 PMC2955839 source

      Not checked in the free run.

    • cites [28] King SL Marks MJ Grady SR Caldarone BJ Koren AO Mukhin AG Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior J Neurosci 2003 23 3837 43 12736354 PMC6742204

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The α7 nicotinic acetylcholine receptor subtype has a critical role in normal refinement of thalamocortical terminals relaying sensory stimulus representations.

    “it has been reported that the α7 nAChR subtype has a critical role in the normal refinement of the thalamocortical terminals which relay sensory stimulus representations from primary thalamic sensory nuclei to layer IV of primary sensory cortex [11, 24–26].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] Metherate R Nicotinic acetylcholine receptors in sensory cortex Learn Mem 2004 11 50 9 14747517

      Not checked in the free run.

    • cites [24] Aramakis VB Metherate R Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex J Neurosci 1998 18 8485 95 9763491 PMC6792829

      Not checked in the free run.

    • cites [25] Aramakis VB Hsieh CY Leslie FM Metherate R A critical period for nicotine-induced disruption of synaptic development in rat auditory cortex J Neurosci 2000 20 6106 16 10934260 PMC6772566

      Not checked in the free run.

    • cites [26] Hsieh CY Leslie FM Metherate R Nicotine exposure during a postnatal critical period alters NR2A and NR2B mRNA expression in rat auditory forebrain Brain Res Dev Brain Res 2002 133 19 25 11850060

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Developmental nicotine exposure alters processing of somatosensory stimuli in adult mice via α4β2α5 nicotinic acetylcholine receptors expressed in corticothalamic projections.

    “We have shown previously that developmental nicotine exposure alters the processing of somatosensory stimuli in adult mice via α4β2α5 nAChRs expressed in corticothalamic projections [27].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Heath CJ King SL Gotti C Marks MJ Picciotto MR Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through alpha4/beta2/alpha5 nicotinic acetylcholine receptors Neuropsychopharmacology 2010 35 2324 38 20736992 PMC2955839 source

      Not checked in the free run.

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

    Study design and conductown data

    There was no statistical difference between the ages of saccharin- and nicotine-treated mice at the beginning of auditory discrimination training.

    “There was no statistical difference between the ages of saccharin- (4.05±0.18 months, mean±SEM) and nicotine-treated (4.54±0.23 months) mice at the beginning of auditory discrimination training (two-tailed t-test of independent samples: t(43)=1.73, p=0.09).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The ages of wild-type and β2 nicotinic acetylcholine receptor knockout mice were not statistically different.

    “The ages of wild-type (4.47±0.27 months) and β2 nAChR knockout (4.84±0.37 months) mice were also not statistically different (two-tailed t-test of independent samples: t(9)=0.78, p=0.46).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Tone frequencies of 12 and 15 kHz are within the optimal hearing range for adult mice.

    “Tone frequencies were selected based on audiograms measured in adult mice and are both well within the optimal hearing range [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Ehret G Development of absolute auditory thresholds in the house mouse (Mus musculus) J Am Audiol Soc 1976 1 179 84 956003

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The absence of the β2 nAChR subunit does not impact the ability of mice to detect the presence of a tone or to withhold magazine approach when no tone is delivered.

    “nor does it appear to impact the ability of mice to detect the presence of a tone or to withhold magazine approach when no tone is delivered.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Outliers were determined by excluding animals with Discrimination Ratios outside 1.5 times the interquartile range on any single day of testing.

    “Outliers were determined by excluding animals with Discrimination Ratios outside of 1.5 x the interquartile range [51] on any single day of testing.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Howell DC Statistical methods for psychology 2002 Pacific Grove Duxbury 5th ed

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The impaired performance observed in auditory discrimination learning was not due to learning impairments or to increases in overall response rates.

    “suggesting that the impaired performance we observed in auditory discrimination learning was not due to learning impairments or to increases in overall response rates.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Several rodent studies have reported increased locomotion in adult mice following perinatal nicotine treatment, although another group found no differences in locomotor activity.

    “Several rodent studies have used open field locomotor activity as a proxy for the hyperactivity observed in this disorder [55], and have reported increased locomotion in adult mice following perinatal nicotine treatment [41, 56, 57], although another group found no differences in locomotor activity [58].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [55] Wickstrom R Effects of nicotine during pregnancy: human and experimental evidence Curr Neuropharmacol 2007 5 213 22 19305804 PMC2656811 source

      Not checked in the free run.

    • cites [41] Pauly JR Sparks JA Hauser KF Pauly TH In utero nicotine exposure causes persistent, gender-dependant changes in locomotor activity and sensitivity to nicotine in C57Bl/6 mice Int J Dev Neurosci 2004 22 329 37 15380832

      Not checked in the free run.

    • cites [56] Ajarem JS Ahmad M Prenatal nicotine exposure modifies behavior of mice through early development Pharmacol Biochem Behav 1998 59 313 8 9476975

      Not checked in the free run.

    • cites [57] Paz R Barsness B Martenson T Tanner D Allan AM Behavioral teratogenicity induced by nonforced maternal nicotine consumption Neuropsychopharmacology 2007 32 693 9 16554741

      Not checked in the free run.

    • cites [58] Chistyakov V Patkina N Tammimaki A Talka R Salminen O Belozertseva I Nicotine exposure throughout early development promotes nicotine self-administration in adolescent mice and induces long-lasting behavioural changes Eur J Pharmacol 2010 640 87 93 20457149

      Not checked in the free run.

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

    Premisecitation

    One of the persistent consequences of gestational tobacco exposure in human children is an elevated risk for developing ADHD.

    “One of the persistent consequences of gestational tobacco exposure in human children is an elevated risk for developing ADHD [7, 52–54].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [7] Nomura Y Marks DJ Halperin JM Prenatal exposure to maternal and paternal smoking on attention deficit hyperactivity disorders symptoms and diagnosis in offspring J Nerv Ment Dis 2010 198 672 8 20823730 PMC3124822

      Not checked in the free run.

    • cites [52] Button TM Maughan B McGuffin P The relationship of maternal smoking to psychological problems in the offspring Early Hum Dev 2007 83 727 32 17888593 PMC2116991

      Not checked in the free run.

    • cites [53] Ernst M Moolchan ET Robinson ML Behavioral and neural consequences of prenatal exposure to nicotine J Am Acad Child Adolesc Psychiatry 2001 40 630 41 11392340

      Not checked in the free run.

    • cites [54] Linnet KM Dalsgaard S Obel C Wisborg K Henriksen TB Rodriguez A Maternal lifestyle factors in pregnancy risk of attention deficit hyperactivity disorder and associated behaviors: review of the current evidence Am J Psychiatry 2003 160 1028 40 12777257 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Enhanced learning has been reported in a fear conditioning task and in performance of passive avoidance, while no differences in learning were observed in a 5-choice serial reaction time paradigm.

    “Contrary to this hypothesis, enhanced learning has been reported in a fear conditioning task [57] and in performance of passive avoidance [27], while no differences in learning were observed in a 5-choice serial reaction time paradigm [32].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [57] Paz R Barsness B Martenson T Tanner D Allan AM Behavioral teratogenicity induced by nonforced maternal nicotine consumption Neuropsychopharmacology 2007 32 693 9 16554741

      Not checked in the free run.

    • cites [27] Heath CJ King SL Gotti C Marks MJ Picciotto MR Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through alpha4/beta2/alpha5 nicotinic acetylcholine receptors Neuropsychopharmacology 2010 35 2324 38 20736992 PMC2955839 source

      Not checked in the free run.

    • cites [32] Schneider T Ilott N Brolese G Bizarro L Asherson PJ Stolerman IP Prenatal exposure to nicotine impairs performance of the 5-choice serial reaction time task in adult rats Neuropsychopharmacology 2011 36 1114 25 21289608 PMC3077278

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The results suggest that either β2-containing nAChRs are critical for normal auditory discrimination learning or that exposure to nicotine during a critical period of development can disrupt the normal expression or function of β2-containing nAChRs at a time when this receptor is necessary for the maturation of neural circuits involved in auditory processing.

    “These results suggest either that β2-containing nAChRs are critical for normal auditory discrimination learning or that exposure to nicotine during a critical period of development can disrupt the normal expression or function of β2-containing nAChRs at a time when this receptor is necessary for the maturation of neural circuits involved in auditory processing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Successful performance of both the auditory discrimination and DRL tasks depends upon behavioral inhibition.

    “Successful performance of both tasks depends upon behavioral inhibition [59]; the auditory discrimination task requires mice to withhold responding to the Unrewarded Tone, while the DRL task requires mice to withhold responding over the 12 sec interval.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Dalley JW Everitt BJ Robbins TW Impulsivity, compulsivity, and top-down cognitive control Neuron 2011 69 680 94 21338879 source

      Not checked in the free run.

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

    Premisecitation

    It is uncertain at what stage in the auditory system aberrant stimulus processing begins to occur, with some studies reporting alterations in auditory brainstem responses in neonates and 6 month old offspring exposed to tobacco in utero and others finding no effect at this level.

    “It is uncertain at what stage in the auditory system aberrant stimulus processing begins to occur, with some studies reporting alterations in auditory brainstem responses in neonates and 6 month old offspring exposed to tobacco in utero [63, 64] and others finding no effect at this level [65].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [63] Kable JA Coles CD Lynch ME Carroll J The impact of maternal smoking on fast auditory brainstem responses Neurotoxicol Teratol 2009 31 216 24 19224709 PMC2693298

      Not checked in the free run.

    • cites [64] Peck JD Neas B Robledo C Saffer E Beebe L Wild RA Intrauterine tobacco exposure may alter auditory brainstem responses in newborns Acta Obstet Gynecol Scand 2010 89 592 6 20367434

      Not checked in the free run.

    • cites [65] Trammer RM Aust G Koster K Obladen M Narcotic and nicotine effects on the neonatal auditory system Acta Paediatr 1992 81 962 5 1290858

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Prefrontal cortex, including anterior cingulate cortex, is implicated in successful DRL performance, but function of the hippocampus and ventral striatum are essential for performance of this task.

    “Prefrontal cortex, including anterior cingulate cortex, is also implicated in successful DRL performance [59, 61], but function of the hippocampus [59, 61] and ventral (rather than dorsal) striatum [59, 62] are essential for performance of this task.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [59] Dalley JW Everitt BJ Robbins TW Impulsivity, compulsivity, and top-down cognitive control Neuron 2011 69 680 94 21338879 source

      Not checked in the free run.

    • cites [61] Cho YH Jeantet Y Differential involvement of prefrontal cortex, striatum, and hippocampus in DRL performance in mice Neurobiol Learn Mem 2010 93 85 91 19703576

      Not checked in the free run.

    • cites [62] Pothuizen HH Jongen-Relo AL Feldon J Yee BK Double dissociation of the effects of selective nucleus accumbens core and shell lesions on impulsive-choice behaviour and salience learning in rats Eur J Neurosci 2005 22 2605 16 16307603

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Previous studies have implicated the anterior cingulate region of prefrontal cortex and the dorsomedial striatum in sensory discrimination when multiple stimuli differentially predict reward and when responding to an unrewarded stimulus must be inhibited.

    “Previous studies have implicated the anterior cingulate region of prefrontal cortex [60] and the dorsomedial striatum [44, 45] in sensory discrimination when multiple stimuli differentially predict reward and when responding to an unrewarded stimulus must be inhibited [59].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [60] Cardinal RN Parkinson JA Marbini HD Toner AJ Bussey TJ Robbins TW Role of the anterior cingulate cortex in the control over behavior by Pavlovian conditioned stimuli in rats Behav Neurosci 2003 117 566 87 12802885

      Not checked in the free run.

    • cites [44] Kimchi EY Laubach M The dorsomedial striatum reflects response bias during learning J Neurosci 2009 29 14891 902 19940185 PMC6666004

      Not checked in the free run.

    • cites [45] Kimchi EY Laubach M Dynamic encoding of action selection by the medial striatum J Neurosci 2009 29 3148 59 19279252 PMC3415331

      Not checked in the free run.

    • cites [59] Dalley JW Everitt BJ Robbins TW Impulsivity, compulsivity, and top-down cognitive control Neuron 2011 69 680 94 21338879 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    There are both similarities and differences in the neural substrates involved in performance of the auditory discrimination and DRL tasks.

    “Consistent with the partial overlap in the behavioral requirements of the two tasks, there are both similarities and differences in the neural substrates involved in their performance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The initial cortical relay of sensory stimuli in nicotine-exposed individuals is likely compromised, which in turn impairs overall sensory processing.

    “Since both the ascending and descending connections between sensory thalamus and primary sensory cortex are vulnerable to nicotine exposure, it is likely that the initial cortical relay of sensory stimuli in nicotine-exposed individuals is compromised which in turn impairs overall sensory processing.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Similar circuitry is present in the auditory and visual systems, and information transfer through the cortex may occur via both cortico-cortical and cortico-thalamo-cortical routes.

    “It has been suggested that similar circuitry is present in the auditory and visual systems and that therefore information transfer through the cortex may occur via both cortico-cortical and cortico-thalamo-cortical routes [68–70].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [68] Theyel BB Llano DA Sherman SM The corticothalamocortical circuit drives higher-order cortex in the mouse Nat Neurosci 2010 13 84 8 19966840 PMC2846438

      Not checked in the free run.

    • cites [69] Reichova I Sherman SM Somatosensory corticothalamic projections: distinguishing drivers from modulators J Neurophysiol 2004 92 2185 97 15140908

      Not checked in the free run.

    • cites [70] Sherman SM The thalamus is more than just a relay Curr Opin Neurobiol 2007 17 417 22 17707635 PMC2753250

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mice lacking the β2 subunit were unimpaired in an auditory-cued fear conditioning paradigm and showed hypersensitivity to a somatosensory stimulus in passive avoidance.

    “For instance, mice lacking the β2 subunit were unimpaired in an auditory-cued fear conditioning paradigm [66] and showed hypersensitivity to a somatosensory stimulus in passive avoidance [27, 28].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [66] Wehner JM Keller JJ Keller AB Picciotto MR Paylor R Booker TK Role of neuronal nicotinic receptors in the effects of nicotine and ethanol on contextual fear conditioning Neuroscience 2004 129 11 24 15489024

      Not checked in the free run.

    • cites [27] Heath CJ King SL Gotti C Marks MJ Picciotto MR Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through alpha4/beta2/alpha5 nicotinic acetylcholine receptors Neuropsychopharmacology 2010 35 2324 38 20736992 PMC2955839 source

      Not checked in the free run.

    • cites [28] King SL Marks MJ Grady SR Caldarone BJ Koren AO Mukhin AG Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior J Neurosci 2003 23 3837 43 12736354 PMC6742204

      Not checked in the free run.

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

    Premisecitation

    This circuit includes a corticothalamic relay from layer VB of primary somatosensory cortex to the posterior medial thalamic nucleus and a thalamocortical relay from this nucleus to layer IV of secondary somatosensory cortex.

    “This circuit includes a corticothalamic relay from layer VB of primary somatosensory cortex to the posterior medial thalamic nucleus and a thalamocortical relay from this nucleus to layer IV of secondary somatosensory cortex [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Theyel BB Llano DA Sherman SM The corticothalamocortical circuit drives higher-order cortex in the mouse Nat Neurosci 2010 13 84 8 19966840 PMC2846438

      Not checked in the free run.

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

    Premisecitation

    A cortico-thalamo-cortical circuit exists between primary and secondary somatosensory cortices that allows information transfer in the absence of direct cortico-cortical connections.

    “For example, it has been reported recently that a cortico-thalamo-cortical circuit exists between primary and secondary somatosensory cortices that allows information transfer in the absence of direct cortico-cortical connections [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Theyel BB Llano DA Sherman SM The corticothalamocortical circuit drives higher-order cortex in the mouse Nat Neurosci 2010 13 84 8 19966840 PMC2846438

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The corticothalamic projections between rodent prefrontal cortex and the medial dorsal thalamic nucleus can be altered by nicotine administration in a slice preparation, suggesting that activity in this higher cortical area can be affected directly by nicotine exposure.

    “For instance, the corticothalamic projections between rodent prefrontal cortex and the medial dorsal thalamic nucleus can be altered by nicotine administration in a slice preparation [67], suggesting that activity in this higher cortical area can be affected directly by nicotine exposure.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Kassam SM Herman PM Goodfellow NM Alves NC Lambe EK Developmental excitation of corticothalamic neurons by nicotinic acetylcholine receptors J Neurosci 2008 28 8756 64 18753377 PMC2909269 source

      Not checked in the free run.

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

    Premisecitation

    Some evidence indicates that nicotine exposure during early development can affect performance in tasks that depend upon higher order cortex, while others have failed to find differences in performance of decision-making tasks.

    “While some evidence indicates that nicotine exposure during early development can affect performance in tasks that depend upon higher order cortex [32], others have failed to find differences in performance of decision-making tasks [38, 71].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [32] Schneider T Ilott N Brolese G Bizarro L Asherson PJ Stolerman IP Prenatal exposure to nicotine impairs performance of the 5-choice serial reaction time task in adult rats Neuropsychopharmacology 2011 36 1114 25 21289608 PMC3077278

      Not checked in the free run.

    • cites [38] Brunzell D Chang J Schneider B Olausson P Taylor J Picciotto M beta2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice Psychopharmacology (Berl) 2006 184 328 38 16133126

      Not checked in the free run.

    • cites [71] Mitchell MR Mendez IA Vokes CM Damborsky JC Winzer-Serhan UH Setlow B Effects of developmental nicotine exposure in rats on decision-making in adulthood Behav Pharmacol 2012 23 34 42 22123182 PMC3253892

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Altered sensory processing can lead to differential stimulus representations in higher cortical areas responsible for executive function and cognitive control and therefore result in altered behavioral responses.

    “Clearly, altered sensory processing can lead to differential stimulus representations in the higher cortical areas responsible for executive function and cognitive control and therefore result in altered behavioral responses”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The β2 nAChR subunit knockout mice exhibited a behavioral profile similar to the nicotine-exposed mice in the auditory discrimination task, suggesting that expression of β2* nAChRs is required for normal sensory processing in adulthood.

    “It is significant that the β2 nAChR subunit knockout mice exhibited a behavioral profile similar to the nicotine-exposed mice in the auditory discrimination task, since it suggests that expression of β2* nAChRs is required for normal sensory processing in adulthood.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Taken together, these data emphasize the critical role of nAChRs in the development of neural circuits involved in sensory processing and that nicotine-mediated disruption of the refinement of this circuitry can have long-lasting consequences for exposed individuals.

    “Taken together, these data emphasize the critical role of nAChRs in the development of neural circuits involved in sensory processing and that nicotine-mediated disruption of the refinement of this circuitry can have long-lasting consequences for exposed individuals.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    Direct adverse effects of developmental nicotine exposure on higher cortical areas cannot be excluded.

    “however, direct adverse effects of developmental nicotine exposure on these higher cortical areas cannot be excluded.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    β2* nAChRs have an essential role in the maturation of the sensory processing circuitry and are dispensable once this process is completed.

    “These data suggest that β2* nAChRs have an essential role in the maturation of the sensory processing circuitry and that it is dispensable once this process is completed [27, 28].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] Heath CJ King SL Gotti C Marks MJ Picciotto MR Cortico-thalamic connectivity is vulnerable to nicotine exposure during early postnatal development through alpha4/beta2/alpha5 nicotinic acetylcholine receptors Neuropsychopharmacology 2010 35 2324 38 20736992 PMC2955839 source

      Not checked in the free run.

    • cites [28] King SL Marks MJ Grady SR Caldarone BJ Koren AO Mukhin AG Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior J Neurosci 2003 23 3837 43 12736354 PMC6742204

      Not checked in the free run.

61 of 61

  • The paper relies on this without support.

    The auditory discrimination task specifically measures auditory stimulus processing rather than other cognitive or motivational processes.

    “This suggests that the auditory discrimination impairments are not a consequence of a general deficit in learning and memory, but may be the result of compromised auditory stimulus processing in the nicotine-exposed and knockout animals.”

  • The paper relies on this without support.

    The differential reinforcement of low rate task does not depend on auditory stimulus processing.

    “later cohorts were also tested in a DRL schedule, which does not depend on auditory stimulus processing.”

  • The paper relies on this without support.

    The DRL schedule assesses learning in a task that does not depend on discrimination between sensory stimuli.

    “This task was used to assess learning in a task that does not depend on discrimination between sensory stimuli and to examine potential differences in impulsive responding”
3 of 3

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?

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.

  • Consistentt(43) = 1.73reported p = .09 · recomputed p = .091

    “t(43)=1.73, p = .09”

  • Consistentt(9) = 0.78reported p = .46 · recomputed p = .455

    “t(9)=0.78, p = .46”

  • Consistentt(48) = -0.93reported p = .36 · recomputed p = .357

    “t(48)=−0.93, p = .36”

3 of 3

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.

  • DRL total response-rate comparison uses the wrong inequality

    Minor

    The text says the fixed-interval group had a higher total response rate, and its reported value is 9.32 versus 7.42. The inequality between those values is reversed.

  • Hit-response comparison uses the wrong inequality

    Minor

    The reported nicotine value, 2.87, is greater than the saccharin value, 2.67, as the group label says, but the inequality between the values says the opposite.

  • DRL burst response-rate comparison uses the wrong inequality

    Minor

    The text says burst responding was higher in the fixed-interval group, and its reported value is 1.76 versus 0.70. The inequality between those values is reversed.

3 of 3

Cites

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Authors
Horst, N. K., Heath, C. J., Neugebauer, N. M., Kimchi, E. Y., Laubach, M., & Picciotto, M. R.
Affiliations
Yale University (US)
Corresponding author
Picciotto, Marina R.
ORCID
Venue
Behavioural Brain Research
Publisher
Elsevier BV
Published
2012-05
Volume
231
Issue
1
Pages
170-180
ISSN
0166-4328 (ISSN-L)
DOI
10.1016/j.bbr.2012.03.002
PMC
PMC3334440
OpenAlex
W2145564975
Semantic Scholar
054b176652a7635b4f2fb11c4856e493ba63c87a
Cited by
17
References
71
Citations by year
2026: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Behavioural Brain Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Open Research Online (The Open University) (submittedVersion)
Funders
  • State of Connecticut Department of Mental Health and Addiction Services
  • Yale University
  • National Institutes of Health (5rl5da024858-05)
  • National Institute on Drug Abuse (DA14241, K02DA000436, RL5-DA024858, IRL5 DA024858, DA 10455, R01DA014241, R29DA010455, R01DA010455, DA 00436, R37DA014241)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords
perinatal nicotine exposure, maternal smoking, auditory discrimination learning, nicotinic acetylcholine receptors, auditory processing, differential reinforcement of low rates, learning and memory, developmental neuroscience
MeSH terms
Acoustic Stimulation, Animals, Animals, Newborn, Auditory Pathways, Auditory Perception, Discrimination Learning, Female, Male, Nicotine, Pregnancy, Receptors, Nicotinic, Mice, Knockout, Nicotinic Agonists, Mice

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 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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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