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Cited by 10Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroendocrine regulation and behavior

Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia

Open access
Achterberg, E. J. Marijke, Biemans, Barbara, Vanderschuren, Louk J. M. J.·2025·Psychopharmacology
DOI 10.1007/s00213-024-06559-zPMC PMC12043747
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Abstract

Rationale: Genetic and environmental factors cause neuropsychiatric disorders through complex interactions that are far from understood. Loss-of-function mutations in synaptic proteins like neurexin1α have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), both characterised by problems in social behaviour. Childhood social play behaviour is thought to facilitate social development, and lack of social play may precipitate or exacerbate ASD and SCZ. Objective: To test the hypothesis that an environmental insult acts on top of genetic vulnerability to precipitate psychiatric-like phenotypes. To that aim, social behaviour in neurexin1α knockout rats was assessed, with or without deprivation of juvenile social play. We also tested drugs prescribed in ASD or SCZ to assess the relevance of this dual-hit model for these disorders. Results: Neurexin1α knockout rats showed an aberrant social phenotype, with high amounts of social play, increased motivation to play, age-inappropriate sexual mounting, and an increase in general activity. Play deprivation subtly altered later social behaviour, but did not affect the phenotype of neurexin1α knockout rats. Risperidone and methylphenidate decreased play behaviour in both wild-type and knockout rats. Amphetamine-induced hyperactivity was exaggerated in neurexin1α knockout rats. Conclusion: Deletion of the neurexin1α gene in rats causes exaggerated social play, which is not modified by social play deprivation. This phenotype therefore resembles disinhibited behaviour rather than the social withdrawal seen in ASD and SCZ. The neurexin1α knockout rat could be a model for inappropriate or disinhibited social behaviour seen in childhood mental disorders.

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Written from the paper’s full text.

TL;DR

Neurexin1α knockout (nrxn1-KO) rats show exaggerated social play, increased motivation for play, age-inappropriate sexual mounting, and hyperactivity, rather than the social withdrawal typical of ASD/SCZ. Juvenile play deprivation subtly altered later social behaviour but did not modify the nrxn1-KO phenotype, and risperidone/methylphenidate reduced play similarly in wild-type and KO rats.

Key findings

  • Nrxn1-KO rats played more than WT rats across development: at 4 weeks, pouncing t(32)=4.01, p<0.001 and pinning t(32)=5.00, p<0.001, with reduced social exploration t(32)=4.70, p<0.001; at 7 weeks, pouncing t(32)=2.60, p=0.01 and pinning t(32)=2.15, p=0.04; at 11 weeks, pouncing t(17)=2.55, p=0.02 and pinning trend p=0.09.
  • Motivation for social play was higher in nrxn1-KO rats: more active lever presses t(7)=-3.14, p=0.02, more rewards t(7)=-3.65, p=0.01, and higher breakpoint Z=-2.46, p=0.01.
  • Age-inappropriate sexual mounting occurred in nrxn1-KO rats: at 4 weeks in 10/16 KO vs 1/18 WT pairs, t(32)=3.18, p=0.003; at 7 weeks in 13/16 KO vs 4/18 WT pairs, t(32)=3.89, p<0.001; at 11 weeks in 6/9 KO vs 0/10 WT pairs, t(32)=2.92, p=0.001.
  • Play deprivation subtly altered adult social behaviour but did not affect the nrxn1-KO phenotype; risperidone and methylphenidate decreased play in both genotypes, and amphetamine-induced hyperactivity was exaggerated in nrxn1-KO rats (genotype×dose F(2,117)=3.17, p=0.046).

Methods

  • Male and female nrxn1-KO and WT Sprague Dawley rats, bred from heterozygous pairs, were tested for social play at PND21–24, PND45–49, and PND75–77; play deprivation consisted of social isolation with a divided cage during PND21–42.
  • Separate cohorts assessed operant responding for social play, adult social behaviour, three-chamber social interest/discrimination, locomotor activity, and drug challenges with risperidone (0, 0.06, 0.2 mg/kg), methylphenidate (0, 0.3, 1.0 mg/kg), and amphetamine (0, 0.25, 0.5 mg/kg), all subcutaneous.
  • Data were analysed with 2- or 3-way ANOVAs, repeated-measures ANOVAs, one-sample t-tests against 50% chance, Friedman tests with Wilcoxon post hoc for breakpoints, and Bonferroni-corrected post hoc tests.

Limitations

  • Stated: the risperidone/methylphenidate cohort and the operant responding experiment used only male rats due to facility/equipment capacity; the authors note that whether reward motivation is generally heightened or specific to play remains to be studied, that the mechanism of reduced mounting after play deprivation remains unidentified, and that an interaction between play deprivation and nrxn1 deletion might require socially challenging encounters rather than the safe settings used.
  • Evident: the paper reports no formal limitations section; the play-deprivation manipulation produced only subtle social alterations and did not robustly interact with genotype, and the study does not directly establish whether the exaggerated play reflects altered social reward, disinhibition, or another mechanism.

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

Integrity signals

Registry

Crossref · 10.1007/s00213-024-06559-z

Cites

118 of 118 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

31 of 82 cited sources checked · 13 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    In mice, only mild phenotypes and varying results have been described in the social spectrum after nrxn1 ablation.

    “but in the social spectrum, only mild phenotypes and varying results have been described (Grayton et al. 2013, Rabaneda et al. 2014, Dachtler et al. 2015; Armstrong et al. 2020).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Grayton et al. 2013

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

    • cites Rabaneda et al. 2014 source

      The ‘Autistic-like Behavior of bNrx1DC Mice’ section reports social deficits in both young and aged mice, including reduced interaction with a novel mouse; the Discussion also describes defects in sociability and social preference. Rather than reporting only mild or varying social findings after nrxn1 ablation, this paper studies mice expressing a mutant neurexin-1b protein and reports deficits replicated across ages. (LLM, conf=0.85)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites Dachtler et al. 2015 source
  • Premisecitation

    Depriving rats of social play behaviour during development results in impairments in the social, emotional and cognitive domains.

    “Indeed, depriving rats of social play behaviour during development results in impairments in the social, emotional and cognitive domains (Vanderschuren and Trezza 2014; Pellis et al. 2023).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Vanderschuren and Trezza 2014 source
    • cites Pellis et al. 2023 source
  • Premisecitation

    The neurexin-1 (nrxn1) gene has been linked directly to ASD and SCZ.

    “Of these, the neurexin-1 (nrxn1) gene has been linked directly to ASD and SCZ (Kim et al. 2008; Rujescu et al. 2009, Glessner et al. 2009; Ching et al. 2010; Gauthier et al. 2011).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites Kim et al. 2008 source

      The paper’s opening section (p. 1) implicates NRXN1 in autism spectrum disorder, supporting the ASD part of the claim. The copy does not link NRXN1 to schizophrenia (SCZ); a search for “schizophrenia” found no such passage. The other citations may support that part, but this verdict concerns Kim et al. only. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Rujescu et al. 2009 source
    • cites Glessner et al. 2009 source

      The paper reports in its main text (indexed under Abstract; page unavailable) that NRXN1 deletions replicate an association with ASD in its cohorts. It does not link NRXN1 to schizophrenia; the schizophrenia association mentioned there concerns ASTN2 deletions. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Interpretationown data

    The strong increase in play behaviour in the nrxn1-KO rats in this study is in contrast to the decrease in play found previously by Kight et al. (2021).

    “The strong increase in play behaviour in the nrxn1-KO rats in our study is in contrast to the decrease in play found previously by Kight et al. (2021).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Kight et al. (2021) source
  • Interpretationreasoning

    Important procedural differences between this study and Kight et al. (2021) may explain the discrepancy in results.

    “there are also important procedural differences, which may explain the discrepancy in the obtained results.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Kight et al. (2021) source
  • Classified as probably not a substantial claim. 42
  • May combine two claims. 34
  • The quote only partly states this claim. 1

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

    Premisecitation

    Previous studies with nrxn1-deficient rats have shown altered patterns of social interest.

    “altered patterns of social interest (Twining et al. 2017)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Twining et al. 2017 source

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

    Premisecitation

    Janz et al. (2022) reported hyperactivity, deficits in context-dependent auditory processing but a normal response towards social stimuli in nrxn1-deficient rats.

    “Janz et al. (2022) reported hyperactivity, deficits in context-dependent auditory processing but a normal response towards social stimuli.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Janz et al. (2022) source

      The Results report locomotor hyperactivity and severe deficits in context-dependent auditory processing in Nrxn1α−/− rats. In “Intact responses to social stimuli” (page not provided), the paper describes social stimulus-driven responses as overall intact, but notes subtle attenuation of beta-band oscillatory power; calling the response simply normal omits that qualification. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Previous studies with nrxn1-deficient rats have shown sex-specific deficits in ultrasonic vocalizations and social play, but unaffected sociability and social discrimination.

    “sex-specific deficits in ultrasonic vocalizations and social play, but unaffected sociability and social discrimination (Kight et al. 2021).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Kight et al. 2021 source

      The Abstract reports reduced ultrasonic vocalizations in both male and female neonatal rats, but a male-specific deficit in juvenile social play. It also reports unaltered sociability and social discrimination. Thus, the claim is supported except for describing the vocalization deficit as sex-specific. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Play behaviour is disrupted during the prodromal phase of SCZ.

    “and play behaviour is disrupted during the prodromal phase of SCZ (Møller and Husby 2000).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Møller and Husby 2000 source

      The Behavioral Dimensions section reports marked, lasting shifts in interests during the initial schizophrenia prodrome, including shifts away from clubs, sports, music, and theater. That supports a change in recreational activities, but the paper does not specifically identify disrupted play behaviour. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Social withdrawal is a prominent negative symptom of SCZ.

    “With regard to human psychopathology, social withdrawal is a prominent negative symptom of SCZ (Marder and Galderisi 2017).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Marder and Galderisi 2017 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Social play is thought to contribute to the development of brain and behaviour.

    “Alongside its pleasurable properties, social play is thought to contribute to the development of brain and behaviour (Panksepp et al. 1984; Graham and Burghardt 2010; Vanderschuren and Trezza 2014; Pellis et al. 2023).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Panksepp et al. 1984 source
    • cites Graham and Burghardt 2010 source
    • cites Vanderschuren and Trezza 2014 source

  • May combine two claims.

    Premisecitation

    In mice, ablation of nrxn1 resulted in detrimental effects on prepulse inhibition and spatial memory, and increased grooming and motor learning.

    “In mice, ablation of nrxn1 resulted in detrimental effects on prepulse inhibition and spatial memory, and increased grooming and motor learning (Etherton et al. 2009; Blundell et al. 2010)”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Etherton et al. 2009 source

      The Results report decreased prepulse inhibition, increased grooming, and enhanced motor learning in neurexin-1α knockout mice. But the Results and Discussion report no change in spatial learning or memory, contrary to the claimed detrimental effect. (LLM, conf=0.91)

      Experimental — accuracy not yet measured
    • cites Blundell et al. 2010 source

      The Introduction reports impaired spatial memory and increased grooming after neuroligin-1 (NL1) deletion, while the Discussion notes increased grooming in neurexin-1-deficient mice. This paper does not attribute the spatial-memory deficit to nrxn1 ablation. Its Results section also reports normal prepulse inhibition and motor learning in NL1 knockout mice, not impaired prepulse inhibition or increased motor learning. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Alterations in the balance between excitatory and inhibitory signalling in neural micro-circuitry have been implicated in social deficits as seen in ASD and SCZ.

    “Importantly, alterations in the balance between excitatory and inhibitory signalling in neural micro-circuitry have been implicated in social deficits as seen in ASD and SCZ (Yizhar et al. 2011).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Yizhar et al. 2011 source

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

    Premisecitation

    Directly stimulating dopaminergic signalling in the nucleus accumbens enhances social play behaviour.

    “and directly stimulating dopaminergic signalling in the nucleus accumbens enhances social play behaviour (Manduca et al. 2016).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Manduca et al. 2016 source

  • Classified as probably not a substantial claim.

    Premisecitation

    The rewarding properties of social play behaviour in rats have been well-documented in place conditioning and operant conditioning setups.

    “The rewarding properties of social play behaviour in rats have been well-documented in place conditioning and operant conditioning setups (Calcagnetti and Schechter 1992; Trezza et al. 2011; Achterberg et al. 2016a,b, 2019).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Calcagnetti and Schechter 1992 source
    • cites Trezza et al. 2011 source

      Section 2.2 reports consistent evidence from place-conditioning studies that social play is rewarding in adolescent rats. The paper also describes operant responding for play in section 3.2, but the lever-pressing example retrieved there concerns chimpanzees; its rat play-reinforcement examples in section 4.2 use a T-maze. It therefore does not fully substantiate the claim about operant conditioning setups in rats. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites Achterberg et al. 2016a,b, 2019

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

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

    Premisecitation

    Dopamine has been implicated in the motivation for social play.

    “Indeed, dopamine has been implicated in the motivation for social play (Achterberg et al. 2015)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Achterberg et al. 2015 source

      The Introduction and the section on prefrontal mechanisms discuss dopamine in relation to social play, but attribute the drugs’ play-suppressing effects to noradrenergic rather than dopaminergic mechanisms. The Neurocircuitry section says future studies could determine whether reduced play reflects a change in motivation; it does not establish dopamine’s role in that motivation. No page number is available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The Kight et al. (2021) study scored behaviour of individual rats, averaged over 4 days of testing in a non-habituated setting.

    “That is, the Kight et al. (2021) study scored behaviour of individual rats, averaged over 4 days of testing in a non-habituated setting.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Kight et al. (2021) source

      The Materials and Methods section (Juvenile Rough-and-Tumble Play Behavior; page unavailable) says videos were scored for each rat and individual scores were averaged across four days. It does not describe the setting as non-habituated; the pairs were allowed to acclimate in the enclosure for two minutes before recording. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Incentive motivation for rewards depends on dopaminergic neurotransmission in the nucleus accumbens.

    “It is well-known that incentive motivation for rewards depends on dopaminergic neurotransmission in the nucleus accumbens (Salamone et al. 2012).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Salamone et al. 2012 source

      The Summary and Conclusions (page not provided) says nucleus accumbens dopamine is important for aspects of appetitive motivation, including effort and cue-instigated approach. But the paper stresses that dopamine is critical for some motivational functions and not others; it does not support the unqualified claim that incentive motivation for rewards depends on it. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    A lack of inhibition in both social and non-social situations has been reported in children diagnosed with ASD.

    “This lack of inhibition in both social and non-social situations has been reported in children diagnosed with ASD (Davidson et al. 2015; Mayes et al. 2017).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Davidson et al. 2015 source

      The Discussion (page not indicated) reports that some children with ASD appeared to have disinhibited social symptoms, although most showed few observed signs of indiscriminate friendliness. The paper addresses social behaviour but does not report a lack of inhibition in non-social situations. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites Mayes et al. 2017 source

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

    Premisecitation

    Methylphenidate reduces social play through both prefrontal and subcortical limbic structures, implying that alongside increased prefrontal inhibition, methylphenidate may also alter the subcortically mediated emotional properties of social play.

    “the subsequent findings that methylphenidate reduces social play through both prefrontal and subcortical limbic structures implies that alongside increased – prefrontal – inhibition, methylphenidate may also alter the – subcortically mediated – emotional properties of social play (Achterberg et al. 2015).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Achterberg et al. 2015 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Deprivation of social play leads to long-lasting impairments in the social, emotional and cognitive domain.

    “previous studies have shown that deprivation of social play leads to long-lasting impairments in the social, emotional and cognitive domain (Baarendse et al. 2013; Bijlsma et al. 2022; Lukkes et al. 2009a; Potegal and Einon 1989; Van den Berg et al. 1999a; Whitaker et al. 2013, for reviews see Vanderschuren and Trezza 2014; Pellis et al. 2023).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Baarendse et al. 2013 source

      The Discussion reports that social-contact deprivation in post-weaning rats produced social deficits lasting into adulthood, and that this study found adult cognitive-control deficits after juvenile social isolation. The paper studied social isolation rather than selective deprivation of play, and the cited passages do not establish long-lasting emotional impairments. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Bijlsma et al. 2022 source

      The Discussion (page not available) reports that juvenile social-play deprivation affected cognition in adult rats even after weeks of unrestricted social interaction, supporting a long-lasting cognitive effect. It does not report lasting social or emotional impairments; it describes those skills as possible benefits of play rather than measured outcomes of this study. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Lukkes et al. 2009a

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

  • May combine two claims.

    Findingown data

    nrxn1-KO rats made significantly more active lever responses than WT rats, while inactive lever responding was similar.

    “When investigating performance on the active an inactive levers separately, nrxn1-KO rats made significantly more active responses than WT rats (t(7)=-3.14, p=0.02, Fig. 2A) whereas responding on the inactive lever was similar in both genotypes (t(7)=-0.74, p=0.48, Fig. 2A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At week 11, nrxn1-KO rats pounced more and tended to pin more than WT rats.

    “At W11, the nrxn1-KO rats pounced more (tpouncing(17)=2.55, p=0.02) and tended to pin more (tpinning(17)=1.83, p=0.09, Fig. 1A,B) than WT rats”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neurexin1α knockout rats show an aberrant social phenotype characterized by high amounts of social play, increased motivation to play, age-inappropriate sexual mounting, and increased general activity.

    “Neurexin1α knockout rats showed an aberrant social phenotype, with high amounts of social play, increased motivation to play, age-inappropriate sexual mounting, and an increase in general activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Social as well as non-social exploration in the operant task was comparable in nrxn1-KO and WT rats.

    “Social as well as non-social exploration in this task was also comparable in nrxn1-KO and WT rats (social exploration: t(7)= 1.10, p=0.31; non-social exploration: t(7)=-0.71, p=0.50, 2F).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The number of mounts was not different between males and females.

    “The number of mounts was not different between males and females.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The inappropriate mounting behaviour started as early as week 4 of age and was still present in adulthood at 11 weeks of age.

    “This mounting behaviour started as early as week 4 of age and was still present in adulthood at 11 weeks of age.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the risperidone experiment, male nrxn1-KO rats played more than WT animals, showing increases in both pouncing and pinning.

    “Consistent with the experiments without drug treatment (see Fig. 1), male nrxn1-KO rats played more than WT animals, showing increases in both pouncing (Fgenotype(1,67)=17.72, p<0.001, 3A) and pinning (Fgenotype(1,67)=12,73, p=0.001, 3B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Methylphenidate suppressed pouncing and pinning, did not affect social exploration, and increased non-social exploration similarly in both genotypes.

    “Treatment with methylphenidate (0-0.3-1.0 mg/kg) suppressed pouncing (Ftreatment(2,67)=19.80, p<0.001, 3E) and pinning (Ftreatment(2,67)=16.53, p<0.001, 3F), social exploration was not affected (Ftreatment(2,67)=1.29, p=0.28; Fgenotype*treatment(2,67)=1.97, p=0.15, 3G) and non-social exploration was increased similarly in both genotypes (Fgenotype*treatment(2,67)=3.01, p=0.06: Ftreatment(2,67)=12.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    In adulthood, female WT rats' locomotor activity was similar to that of males.

    “but in adulthood, their locomotor activity was similar to that of males.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Females of both genotypes spent more time following than males.

    “and females of both genotypes spent more time following than males.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In adulthood (7 months), similar levels of social approach behaviour and intact social discrimination were seen in the three-chamber task.

    “In adulthood (7 months), similar levels of social approach behaviour as well as intact social discrimination were seen in the three-chamber task.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Both the initiation to play (pouncing) and the number of pins were higher in juvenile (4 weeks) and adolescent (7 weeks) nrxn1-KO rats.

    “Both the initiation to play, pouncing, as well as the number of pins were higher in juvenile (4 weeks), and adolescent (7 weeks) nrxn1-KO rats”
    Quote in the paperSubstantial claim

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

    Findingown data

    There were no differences between male and female rats in social play.

    “Because there were no differences between male and female rats, the data were pooled.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Social exploration and anogenital investigation were not influenced by genotype or sex.

    “These parameters were not influenced by genotype or sex.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Social play deprivation did not affect play behaviour in adulthood; pinning and pouncing were similar between housing conditions.

    “Social play deprivation did not affect play behaviour in adulthood, both pinning and pouncing were similar between housing conditions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Play deprivation subtly affected social behaviour in adulthood, but did not profoundly influence the nrxn1-KO phenotype.

    “Play deprivation subtly affected social behaviour in adulthood, but did not profoundly influence the nrxn1-KO phenotype.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Pouncing was similar between the sexes.

    “Pouncing was similar between the sexes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the social discrimination phase, all groups spent slightly more than 50% of their time with the novel rat compared to the familiar one, but only play-deprived nrxn1-KO rats did so significantly.

    “all groups spent slightly more than 50% of their time with the novel rat compared to the familiar one, but only significantly so in play-deprived nrxn1-KO rats”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Locomotor activity was higher in nrxn1-KO rats compared to WT rats after treatment with vehicle and the 0.5 mg/kg dose of amphetamine, but not the 0.25 mg/kg dose.

    “Post hoc analysis revealed that locomotor activity was higher in nrxn1-KO rats compared to WT rats after treatment with vehicle (t(38)=-2.86, p=0.007) and the 0.5 mg/kg dose of amphetamine (t(39)=-3.43, p=0.001), but not the 0.25 mg/kg dose of amphetamine (t(42)=-1.54, p=0.13).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Risperidone affected non-social exploration differently in the two genotypes: enhanced after low dose in WT, and by both doses in KO.

    “Risperidone affected non-social exploration differently in the two genotypes (Fgenotype*treatment(2,67)=3.23, p=0.05; Ftreatment(2,67)=11.73, p<0.001). Non-social exploration was enhanced after treatment with the low but not the higher dose of risperidone in WT rats whereas it was enhanced by both doses in KO rats”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Females were more active than males in adolescence and adulthood.

    “and females were more active than males (adolescence: Fsex(1,90)=17.08, p<0.001; adulthood: Fsex(1,43)=15.21, p<0.001)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Methylphenidate suppressed pinning in both genotypes, with an interaction effect of genotype and treatment.

    “An interaction effect of genotype and treatment was found for the frequency of pinning (Fgenotype*treatment(2,67)=3.25, p=0.04), methylphenidate suppressed pinning in both genotypes”
    Quote in the paperNot a substantial claim

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

    Findingown data

    There was no difference in amphetamine response between socially housed and play-deprived rats.

    “There was no difference between socially housed and play-deprived rats, therefore these data were pooled.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mounts in play-deprived animals were almost absent and not different between genotypes.

    “while mounts in play-deprived animals were almost absent, and not different between genotypes”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the methylphenidate experiment, male nrxn1-KO rats played more than WT rats, social exploratory behaviour was significantly reduced, and non-social exploration was unaffected.

    “Again, male nrxn1-KO rats played more than WT rats (pouncing: Fgenotype(1,67)=38.98, p<0.001; pinning: Fgenotype(1,67)=27.50, p<0.001) while social exploratory behaviour was significantly reduced (Fgenotype(1,67)=45.10, p<0.001) and non-social exploration was unaffected (Fgenotype(1,67)=0.77, p=0.38).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Female WT rats showed more locomotor activity compared to male WT rats in adolescence.

    “Female WT rats also showed more locomotor activity compared to male WT rats in adolescence”
    Quote in the paperNot a substantial claim

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

    Findingown data

    In adulthood, females made more pins than males.

    “whereas males and females played in equal amounts in adolescence, females made more pins in adulthood compared to males.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Risperidone did not affect social exploration in WT and nrxn1-KO rats.

    “the fact that risperidone did not affect social exploration and increases non-social exploration indicates that at the doses tested, the reduction in social play cannot be explained by general sedative effect of D2 receptor blockade.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Taken together, play deprivation resulted in subtle social alterations but did not act synergistically to produce a specific or more severe social phenotype.

    “Taken together, play deprivation resulted in subtle social alterations but did not act synergistically to produce a specific or more severe social phenotype.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Play has been shown to be impaired in children with ASD.

    “Furthermore, play has been shown to be impaired in children with ASD (Jarrold 2003; Manning and Wainwright 2010)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Jarrold 2003 source
    • cites Manning and Wainwright 2010 source

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

    Study design and conductreasoning

    Breakpoints were analysed using the non-parametric Friedman test, followed by a post hoc Wilcoxon signed ranks test when appropriate.

    “Therefore, breakpoints were analysed using the non-parametric Friedman test, followed by a post hoc Wilcoxon signed ranks test when appropriate.”
    Quote in the paperNot a substantial claim

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

    Study design and conductcitation

    Drug doses were selected based on previous research.

    “Drug doses were carefully selected based on previous research (Vanderschuren et al. 2008; Achterberg et al. 2014; Roche in house data), and doses were calculated as salt.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Vanderschuren et al. 2008 source
    • cites Achterberg et al. 2014

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

    • cites Roche in house data

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

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

    Study design and conductnone given

    Post hoc analysis was performed using Bonferroni correction.

    “Where appropriate, post hoc analysis was performed using one-way ANOVAs and paired or unpaired Students T-tests with Bonferroni correction.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Previous studies with nrxn1-deficient rats have shown profound impairments in attention and cognitive capacities, as well as hyperactivity.

    “Previous studies with nrxn1-deficient rats have shown profound impairments in attention and cognitive capacities, as well as hyperactivity (Esclassan et al. 2015)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Esclassan et al. 2015 source

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

    Premisecitation

    Impaired social play in ASD is thought to intensify the disorder.

    “and impaired social play in ASD is thought to intensify the disorder (Jordan 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jordan 2003 source

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Behaviour was scored live by an observer blind to genotype and housing condition.

    “The behaviour of the animals was digitally recorded and scored live by an observer blind to genotype and housing condition.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Increased social interest, as well as reduced anxiety in the open field, was reported in rats in which the nrxn1 gene was down-regulated in the medial prefrontal cortex.

    “Recently, increased social interest, as well as reduced anxiety in the open field, was reported in rats in which the nrxn1 gene was down-regulated in the medial prefrontal cortex (Wu et al. 2023).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wu et al. 2023

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

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

    Premisecitation

    Neurexin-neuroligin complexes are thought to mediate synaptic signalling, specification and maintenance, and to control the balance of inhibitory GABAergic and excitatory glutamatergic neurotransmission.

    “These neurexin-neuroligin complexes are thought to mediate synaptic signalling, specification and maintenance, and to control the balance of inhibitory GABAergic and excitatory glutamatergic neurotransmission (Südhof 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Südhof 2008 source

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

    Study design and conductnone given

    Pups were genotyped by toe-clipping or ear-punching for genotypic validation.

    “Pups were toe-clipped on post-natal day (PND) 7-9 or ear-punched on PND14 for genotypic validation and weaned between PND21-24.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    It may be that nrxn1-KO rats are more aroused by the encounter with a conspecific after the isolation.

    “It may therefore be that nrxn1-KO rats are more aroused by the encounter with a conspecific after the isolation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The increase in social play behaviour in nrxn1-KO rats was not observed in reinforced trials because in the operant conditioning setup animals have only one minute to play per reinforced period.

    “This is because the operant conditioning setup, animals have only one minute to play per reinforced period”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The possibility that risperidone suppresses social play behaviour through distinct pharmacological mechanisms in the two genotypes can as yet not be excluded.

    “That said, the possibility that risperidone suppresses social play behaviour through distinct pharmacological mechanisms in the two genotypes can as yet not be excluded.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Deletion of the nrxn1 gene results in a socially disinhibited phenotype, rather than hyperactivity non-specifically enhancing any behaviour likely to occur in a given setting.

    “Therefore, we interpret our findings as that deletion of the nrxn1 gene results in a (socially) disinhibited phenotype, rather than that the hyperactivity of the nrxn1-KO rats non-specifically enhances any behaviour likely to occur in a given setting.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    For an interaction between play deprivation and nrxn1 deletion to become apparent, socially challenging encounters need to be assessed, rather than the relatively safe social settings used here.

    “It may therefore be that for an interaction between play deprivation and nrxn1 deletion to become apparent, socially challenging encounters need to be assessed, rather than the relatively safe social settings used here.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The relatively safe social settings used here are not socially challenging.

  • May combine two claims.

    Interpretationreasoning

    The play-suppressant effect of risperidone likely depends on blockade of dopamine D2 receptors, alpha-1 adrenoceptors, or both, and the activity of these receptor systems does not differ between WT and nrxn1-KO rats.

    “Thus, the play-suppressant effect of risperidone likely depends on blockade of dopamine D2 receptors, alpha-1 adrenoceptors, or both, whereby the activity of these receptor systems does not differ between WT and nrxn1-KO rats.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Risperidone exerts its effects through antagonism of dopamine D2 and serotonin 5-HT2 receptors, and also antagonizes noradrenergic alpha-1 and -2 and histaminergic H1 receptors.

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

    Premisecitation

    In challenging social situations, such as an encounter with an aggressive animal, play-deprived animals are less able to use appropriate social signals to manage conflict.

    “previous studies have shown that in challenging social situations, such as in an encounter with an aggressive animal, play-deprived animals are less able to use the appropriate social signals to manage conflict (Van den Berg et al. 1999a, b, c; Von Frijtag et al. 2002).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Van den Berg et al. 1999a

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

    • cites Von Frijtag et al. 2002 source

  • May combine two claims.

    Premisecitation

    Both novelty-induced locomotor activity and the hyperactivity evoked by amphetamine depend on nucleus accumbens dopamine neurotransmission.

    “Given that both novelty-induced locomotor activity (Hooks and Kalivas 1994) and the hyperactivity evoked by amphetamine depend on nucleus accumbens dopamine neurotransmission (Creese and Iversen 1975; Pijnenburg et al. 1975)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Hooks and Kalivas 1994 source
    • cites Creese and Iversen 1975 source
    • cites Pijnenburg et al. 1975 source

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

    Premisecitation

    The play-suppressant properties of methylphenidate are due to increased behavioural inhibition, whereby energetic behaviours that result in diminished attention for the environment are reduced.

    “We have previously argued that the play-suppressant properties of methylphenidate are due to increased behavioural inhibition, whereby energetic behaviours that result in diminished attention for the environment are reduced (Vanderschuren et al. 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Vanderschuren et al. 2008 source

  • May combine two claims.

    Premisecitation

    Treatment with dopamine D2 and alpha-1 receptor antagonists inhibits social play, whereas treatment with an alpha-2 adrenoceptor antagonist enhances it.

    “Treatment with dopamine D2 and alpha-1 receptor antagonists has previously been shown to inhibit social play, whereas treatment with an alpha-2 adrenoceptor antagonist actually enhances it (Siviy et al. 1994; -1996).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Siviy et al. 1994 source
    • cites Siviy et al. 1996 source

  • May combine two claims.

    Premisecitation

    Treatment with methylphenidate in a social setting does not alter locomotion, yet suppresses social play.

    “we have previously shown that treatment with methylphenidate in a social setting does not alter locomotion, yet suppresses social play (Vanderschuren et al. 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Vanderschuren et al. 2008 source

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

    Interpretationcitation

    The specific reduction in social play after methylphenidate treatment is consistent with previous findings.

    “This specific reduction in social play after methylphenidate treatment is consistent with previous findings (Beatty et al. 1982; Vanderschuren et al. 2008)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Beatty et al. 1982 source
    • cites Vanderschuren et al. 2008 source

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

    Premisecitation

    Increased sensitivity of mesolimbic dopamine has been observed in the methylazoxymethanol acetate model of SCZ.

    “it has also been observed in the methylazoxymethanol acetate model of SCZ (e.g. Gomes et al. 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gomes et al. 2014

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

  • Classified as probably not a substantial claim.

    Premisecitation

    Increased sensitivity of mesolimbic dopamine has been implicated in SCZ.

    “Increased sensitivity of mesolimbic dopamine has been implicated in SCZ (Kapur 2003)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kapur 2003 source

  • May combine two claims.

    Interpretationreasoning

    A disinhibited phenotype could underlie the exaggerated social play in nrxn1-KO rats, but it is not one that results from altered noradrenergic neurotransmission.

    “A disinhibited phenotype could therefore underlie the exaggerated social play in nrxn1-KO rats, but it is not one that results from altered noradrenergic neurotransmission.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    These findings on social behaviour are somewhat consistent with previous studies that reported modest reductions in social exploratory behaviour after play deprivation.

    “These findings on social behaviour are somewhat consistent with previous studies, that reported modest reductions in social exploratory behaviour after play deprivation (Hol et al. 1999; Van den Berg et al. 1999a, b, c; Lukkes et al. 2009a,b).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Hol et al. 1999 source
    • cites Van den Berg et al. 1999a

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

    • cites Lukkes et al. 2009a

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

71 of 71

  • The paper relies on this without support.

    Risperidone and methylphenidate are commonly used for symptom management in ASD and SCZ.

    “by testing risperidone and methylphenidate, drugs commonly used for symptom management in ASD and SCZ”

  • The paper relies on this without support.

    Amphetamine exacerbates symptoms of SCZ.

    “as well as amphetamine, that exacerbates symptoms of SCZ”

  • The paper relies on this without support.

    Disruptions in the genes coding for the transsynaptic communication protein neurexin-1 are a risk factor for neurodevelopmental disorders.

    “Proper social functioning, important throughout life, is impaired in neurodevelopmental disorders of which disruptions in the genes coding for the transsynaptic communication protein neurexin-1 is a risk factor.”

  • The authors state this as an assumption.

    Psychiatric symptomatology is precipitated by life events in genetically predisposed individuals.

    “on the basis of the idea that psychiatric symptomatology is precipitated by life events in genetically predisposed individuals”

  • The paper relies on this without support.

    Inappropriate social and sexual behaviour feature in autism spectrum disorder.

    “it is interesting to note that inappropriate social and sexual behaviour also feature in ASD.”

  • The paper relies on this without support.

    The relatively safe social settings used here are not socially challenging.

    “rather than the relatively safe social settings used here.”

  • The paper relies on this without support.

    Risperidone exerts its effects through antagonism of dopamine D2 and serotonin 5-HT2 receptors, and also antagonizes noradrenergic alpha-1 and -2 and histaminergic H1 receptors.

    “This antipsychotic is thought to exert its effects through antagonism of dopamine D2 and serotonin 5-HT2 receptors, but it also antagonizes noradrenergic alpha-1 and -2 and histaminergic H1 receptors.”

  • The paper relies on this without support.

    Amphetamine stimulates the release of dopamine, noradrenaline and serotonin.

    “amphetamine (that stimulates the release of dopamine, noradrenaline and serotonin)”
8 of 8

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(7) = -3.14reported p = .02 · recomputed p = .016

    “t(7)=-3.14, p = .02”

  • Consistentt(7) = -0.74reported p = .48 · recomputed p = .483

    “t(7)=-0.74, p = .48”

  • Consistentt(7) = -3.65reported p = .01 · recomputed p = .008

    “t(7)=-3.65, p = .01”

  • Consistentz = -2.46reported p = .01 · recomputed p = .014

    “(Z=-2.46, p = .01”

  • Consistentt(7) = 0.2reported p = .85 · recomputed p = .847

    “t(7)=0.20, p = .85”

  • Consistentt(7) = 0.28reported p = .79 · recomputed p = .788

    “t(7)=0.28, p = .79”

  • Consistentt(7) = 1.1reported p = .31 · recomputed p = .308

    “t(7)= 1.10, p = .31”

  • Consistentt(7) = -0.71reported p = .5 · recomputed p = .501

    “t(7)=-0.71, p = .50”

  • Consistentt(21) = -2.92reported p = .008 · recomputed p = .008

    “t(21)=-2.92, p = .008”

  • Consistentt(23) = -3.59reported p = .005 · recomputed p = .002

    “t(23)=-3.59, p = .005”

    The paper states a correction for multiple tests

  • Consistentt(23) = -2.32reported p = .04 · recomputed p = .030

    “t(23)=-2.32, p = .04”

    The paper states a correction for multiple tests

  • Consistentt(38) = -2.86reported p = .007 · recomputed p = .007

    “t(38)=-2.86, p = .007”

  • Consistentt(39) = -3.43reported p = .001 · recomputed p = .001

    “t(39)=-3.43, p = .001”

  • Consistentt(42) = -1.54reported p = .13 · recomputed p = .131

    “t(42)=-1.54, p = .13”

14 of 14

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.

  • Vehicle-group t-test degrees of freedom do not match its sample sizes

    Minor

    The amphetamine figure lists 20 vehicle-treated WT and 18 vehicle-treated knockout rats. An independent two-group t-test with those sample sizes has 36 degrees of freedom, not the reported 38; the reported degrees of freedom for the other two dose comparisons do match their listed sample sizes.

  • Methylphenidate's effect on non-social exploration is described both ways

    Minor

    The discussion says methylphenidate did not affect non-social exploration, but the results report a significant treatment effect and an increase at 1.0 mg/kg.

  • Week-11 mounting test has incompatible degrees of freedom

    Minor

    The week-11 tests for the other behaviours use 17 degrees of freedom, consistent with the stated 10 WT and 9 knockout pairs. The mounting test instead reports 32 degrees of freedom.

  • Intact social discrimination is claimed despite nonsignificant results in most groups

    Minor

    The discussion describes social discrimination in the three-chamber task as intact, whereas the results say only play-deprived knockout rats significantly discriminated between familiar and unfamiliar rats.

  • Adult age is labelled with adolescent postnatal days

    Minor

    Figure 4 labels its 11-week adult group PND38-40, whereas the paper identifies PND38-40 as six weeks and 11 weeks as PND75-77.

  • Resocialization interval is incorrectly stated for all play-deprived rats

    Minor

    The results say the animals were resocialized for four days before testing. The methods instead specify 24 hours for cohorts 1 and 3 and four days only for cohort 4.

6 of 6

Cites

Flagged first, then by citations

1 of the 119 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Pellis SM, Pellis VC (2009) The Playful Brain. OneWorld Publications, Oxford, UK
  2. Shields H (1980) Genetics and mental development. In: Child Psychiatry: Modern Approaches, Rutter, M. (ed). Oxford: Blackwell Scientific

Cited by

Sorted by citations

Related

Authors
Achterberg, E. J. M., Biemans, B., & Vanderschuren, L. J. M. J.
Affiliations
  • Utrecht University (NL)
  • Roche (Switzerland) (CH)
Corresponding author
Achterberg, E. J. Marijke
ORCID
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2024-02-29
Volume
242
Issue
5
Pages
1069-1089
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-024-06559-z
PMC
PMC12043747
OpenAlex
W4392292609
Semantic Scholar
63dce4487e92dd5ab9d05d22fd5a26dd1cf64310
Cited by
9
References
119
Citations by year
2026: 4 · 2025: 4 · 2024: 1
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychopharmacology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
F. Hoffmann-La Roche
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
knockout rats, social behavior, autism spectrum disorder, schizophrenia, social play, play deprivation, synaptic proteins, risperidone, methylphenidate, amphetamine-induced hyperactivity, genetic susceptibility, environmental insults
MeSH terms
Autism Spectrum Disorder, Amphetamine, Animals, Autistic Disorder, Behavior, Animal, Disease Models, Animal, Male, Nerve Tissue Proteins, Schizophrenia, Social Behavior, Antipsychotic Agents, Cell Adhesion Molecules, Neuronal, Risperidone, Rats

About these checks

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

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-12.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.

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.

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

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