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Models of Autism and Methods for Assessing Autistic-Like Behavior in Animals

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Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Autistic spectrum disorders (ASD), including autism, constitute a wide range of states and are associated with deficit to social communications, limited interests, and stereotypical behavior. The development of translational medicine and personalized approaches to the treatment of ASD combine the efforts of clinicians and basic scientists and push the direction of studies towards the molecular and genetic mechanisms of developmental disorders and the search for new marker molecules for targeted correction of these states, which are impossible without use of models of ASD in animals, especially rodents. This review describes the key genetic and pharmacological models of ASD in rodents which are actively utilized in experimental studies, along with the most important behavioral tests for assessing deficits in social behavior, stereotypy, and autism-like states in experimental animals.

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References

  • Akther, S., Huang, Z., Liang, M., et al., “Paternal retrieval behavior regulated by brain estrogen synthetase (aromatase) in mouse sires that engage in communicative interactions with pairmates,” Front. Neurosci., 9, 450, 1–12 (2015).

    Google Scholar 

  • Akther, S., Korshnova, N., Zhong, J., et al., “CD38 in the nucleus accumbens and oxytocin are related to paternal behavior in mice,” Mol. Brain, 6, 41, 1–10 (2013).

    Google Scholar 

  • Al-amin, M., Rahman, M., Khan, F. R., et al., “Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism,” Behav. Brain Res., 286, 112–121 (2015).

    CAS  PubMed  Google Scholar 

  • Aronoff, E., Hillyer, R., and Leon, M., “Environmental Enrichment Therapy for Autism: Outcomes with Increased Access,” Neural Plast., 2016, 1–23 (2016).

    Google Scholar 

  • Bambini-Junior, V., Rodrigues, L., Behr, G. A., et al., “Animal model of autism induced by prenatal exposure to valproate: Behavioral changes and liver parameters,” Brain Res., 1408, 8–16 (2011).

    CAS  PubMed  Google Scholar 

  • Baronio, D., Castro, K., Gonchoroski, T., et al., “Effects of an H3R Antagonist on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid,” PLoS One, 10, No. 1, 1–11 (2015).

    Google Scholar 

  • Barrett, C. E., Hennessey, T. M., Gordon, K. M., et al., “Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally,” Mol. Autism, 8, 42, 1–17 (2017).

    Google Scholar 

  • Bauman, M. and Kemper, T. L., “Histoanatomic observations of the brain in early infantile autism,” Neurology, 35, No. 6, 866–874 (1985).

    CAS  PubMed  Google Scholar 

  • Bausch, A. E., Ehinger, R., Straubinger, J., et al., “Loss of sodium-activated potassium channel Slack and FMRP differentially affect social behavior in mice,” Neuroscience, 384, 361–374 (2018).

    CAS  PubMed  Google Scholar 

  • Bromley, R. L., Mawer, G. E., Briggs, M., et al., “The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs,” J. Neurol. Neurosurg. Psychiatry, 84, No. 6, 637–643 (2013).

    PubMed  PubMed Central  Google Scholar 

  • Cai, Y., Wang, L., Xiao, R., et al., “Autism-like behavior in the BTBR mouse model of autism is improved by propofol,” Neuropharmacology, 118, 175–187 (2017).

    CAS  PubMed  Google Scholar 

  • Campolongo, M., Kazlauskas, N., Falasco, G., et al., “Sociability deficits after prenatal exposure to valproic acid are rescued by early social enrichment,” Mol. Autism, 9, 36 (2018).

    PubMed  PubMed Central  Google Scholar 

  • Chang, Y. C., Cole, T. B., and Costa, L. G., “Behavioral phenotyping for autism spectrum disorders in mice,” Curr. Protoc. Toxicol., 72, 1–21 (2017).

    Google Scholar 

  • Chao, O. Y., Yunger, R., and Yang, Y., “Behavioral assessments of BTBR T + Itpr3tf/J mice by tests of object attention and elevated open platform: Implications for an animal model of psychiatric comorbidity in autism,” Behav. Brain Res., 347, 140–147 (2018).

    PubMed  Google Scholar 

  • Cherepanov, S. M., Yokoyama, S., Mizuno, A., et al., “Structure-specific effects of lipidated oxytocin analogs on intracellular calcium levels, parental behavior, and oxytocin concentrations in the plasma and cerebrospinal fluid in mice,” Pharmacol. Res. Perspect., 5, 1, e00290 (2017).

    PubMed  PubMed Central  Google Scholar 

  • Cho, H., Kim, C. H., Knight, E. Q., et al., “Changes in brain metabolic connectivity underlie autistic-like social deficits in a rat model of autism spectrum disorder,” Sci. Rep., 7, 13213 (2017).

    PubMed  PubMed Central  Google Scholar 

  • Choi, C. S., Gonzales, E. L., Kim, K. C., et al., “The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy,” Sci. Rep., 6, 1–11 (2016).

    CAS  Google Scholar 

  • Choi, J., Lee, S., Won, J., et al., “Pathophysiological and neurobehavioral characteristics of a propionic acid-mediated autism-like rat model,” PLoS One, 13, No. 2, 1–17 (2018).

    Google Scholar 

  • Clifford, S., Dissanayake, C., Bui, Q. M., et al., “Autism spectrum phenotype in males and females with fragile X full mutation and premutation,” J. Autism Dev. Disord., 37, 738–747 (2007).

    PubMed  Google Scholar 

  • Crawley, J. N., “Designing mouse behavioral tasks relevant to autistic-like behaviors,” Ment. Retard. Dev. Disabil. Res. Rev., 10, No. 4, 248–258 (2004).

    PubMed  Google Scholar 

  • Crawley, J. N., Chen, T., Puri, A., et al., “Social approach behaviors in oxytocin knockout mice: Comparison of two independent lines tested in different laboratory environments,” Neuropeptides, 41, No. 3, 145–163 (2007).

    CAS  PubMed  Google Scholar 

  • Cristiano, C., Pirozzi, C., Coretti, L., et al., “Palmitoylethanolamide counteracts autistic-like behaviours in BTBR T+tf/J mice: Contribution of central and peripheral mechanisms,” Brain Behav. Immun., 74, 166–175 (2018).

    CAS  PubMed  Google Scholar 

  • Cuevas-Olguin, R., Roychowdhury, S., Banerjee, A., et al., “Cerebrolysin prevents deficits in social behavior, repetitive conduct, and synaptic inhibition in a rat model of autism,” J. Neurosci. Res., 95, No. 12, 2456–2468 (2017).

    CAS  PubMed  Google Scholar 

  • Deacon, R. M. J. and Rawlins, J. N. P., “T-maze alternation in the rodent,” Nat. Protoc., 1, 1 (2006).

    Google Scholar 

  • Du, L., Zhao, G., Duan, Z., and Li, F., “Behavioral improvements in a valproic acid rat model of autism following vitamin D supplementation,” Psychiatry Res., 253, 28–32 (2017).

    CAS  PubMed  Google Scholar 

  • Dufour-Rainfray, D., Vourc’h, P., Le Guisquet, A. M., et al., “Behavior and serotonergic disorders in rats exposed prenatally to valproate: A model for autism,” Neurosci. Lett., 470, No. 1, 55–59 (2010).

    CAS  PubMed  Google Scholar 

  • Edalatmanesh, M. A., Nikfarjam, H., Vafaeec, F., and Moghadas, M., “Increased hippocampal cell density and enhanced spatial memory in the valproic acid rat model of autism,” Brain Res., 1526, 15–25 (2013).

    CAS  PubMed  Google Scholar 

  • El-Ansary, A. K., Bacha, A. B., and Kotb, M., “Etiology of autistic features: the persisting neurotoxic effects of propionic acid,” J. Neuroinflammation, 9, 74, 1–14 (2012).

    Google Scholar 

  • El-Ansary, A. K., Ben Bacha, A. G., and Al-Ayahdi, L. Y., “Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia,” Lipids Health Dis., 10, No. 63, 1–9 (2011).

    Google Scholar 

  • Faraji, J., Karimi, M., Lawrence, C., et al., “Non-diagnostic symptoms in a mouse model of autism in relation to neuroanatomy: the BTBR strain reinvestigated,” Transl. Psychiatry, 8, 1, 1–18 (2018).

    Google Scholar 

  • Foley, A. G., Gannon, S., Rombach-Mullan, N., et al., “Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder,” Neuropharmacology, 63, No. 4, 750–760 (2012).

    CAS  PubMed  Google Scholar 

  • Foley, K. A., MacFabe, D. F., Vaz, A., et al., “Sexually dimorphic effects of prenatal exposure to propionic acid and lipopolysaccharide on social behavior in neonatal, adolescent, and adult rats: Implications for autism spectrum disorders,” Int. J. Dev. Neurosci., 39, 68–78 (2014).

    CAS  PubMed  Google Scholar 

  • Galvez, R. and Greenough, W. T., “Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome,” Am. J. Med. Genet., A135, No. 2, 155–160 (2005).

    Google Scholar 

  • Gholizadeh, S., Arsenault, J., Cong, I., et al., “Reduced phenotypic severity following adeno-associated virus-mediated Fmr1 gene delivery in fragile X mice,” Neuropsychopharmacology, 39, No. 13, 3100–3111 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ha, S., Park, H., Mahmood, U., et al., “Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPAinduced autism mouse model,” Behav. Brain Res., 317, 479–484 (2017).

    CAS  PubMed  Google Scholar 

  • Hammock, E. A. D., “Developmental perspectives on oxytocin and vasopressin,” Neuropsychopharmacology, 40, No. 1, 24–42 (2015).

  • Hara, Y., Ago, Y., Higuchi, M., et al., “Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism,” Horm. Behav., 96, 130–136 (2017).

    CAS  PubMed  Google Scholar 

  • Hara, Y., Ago, Y., Taruta, A., et al., “Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism,” Autism Res., 9, 9, 926–939 (2016).

    PubMed  Google Scholar 

  • Higashida, H., Lopatina, O., Yoshihara, T., et al., “Oxytocin signal and social behaviour: Comparison among adult and infant oxytocin, oxytocin receptor and CD38 gene knockout mice,” J. Neuroendocrinol., 22, No. 5, 373–379 (2010).

    CAS  PubMed  Google Scholar 

  • Higashida, H., Yokoyama, S., Huang, J. J., et al., “Social memory, amnesia, and autism: Brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38,” Neurochem. Int., 61, No. 6, 828–838 (2012).

    CAS  PubMed  Google Scholar 

  • Higashida, H., Yokoyama, S., Munesue, T., et al., “CD38 gene knockout juvenile mice: A model of oxytocin signal defects in autism,” Biol. Pharm. Bull., 34, No. 9, 1369–1372 (2011).

    CAS  PubMed  Google Scholar 

  • Hirsch, M. M., Deckmann, I., Fontes-Dutra, M., et al., “Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA,” Food Chem. Toxicol., 115, 336–343 (2018).

    CAS  PubMed  Google Scholar 

  • Jacobs, S., Huang, F., Tsien, J., and Wei, W., “Social recognition memory test in rodents,” Bio-Protocol, 6, No. 9, 1–12 (2016).

    CAS  Google Scholar 

  • Jin, D., Liu, H. X., Hirai, H., et al., “CD38 is critical for social behaviour by regulating oxytocin secretion,” Nature, 446, No. 7131, 41–45 (2007).

    CAS  PubMed  Google Scholar 

  • Jory, J., “Abnormal fatty acids in Canadian children with autism,” Nutrition, 32, No. 4, 474–477 (2016).

    CAS  PubMed  Google Scholar 

  • Kang, J. and Kim, E., “Suppression of NMDA receptor function in mice prenatally exposed to valproic acid improves social deficits and repetitive behaviors,” Front. Mol. Neurosci., 8, 17, 1–9 (2015).

    Google Scholar 

  • Kataoka, S., Takuma, K., Hara, Y., et al., “Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid,” Int. J. Neuropsychopharmacol., 16, No. 1, 91–103 (2013).

    CAS  PubMed  Google Scholar 

  • Kazdoba, T. M., Leach, P. T., Silverman, J. L., and Crawley, J. N., “Modeling fragile X syndrome in the Fmr1 knockout mouse,” Intractable Rare Dis. Res., 3, No. 4, 118–133 (2014).

    PubMed  PubMed Central  Google Scholar 

  • Kim, J. W., Seung, H., Kim, K. C., et al., “Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism,” Neuropharmacology, 113, 71–81 (2017).

    CAS  PubMed  Google Scholar 

  • Kim, K. C., Kim, P., Go, H. S., et al., “Male-specific alteration in excitatory post-synaptic development and social interaction in pre-natal valproic acid exposure model of autism spectrum disorder,” J. Neurochem., 124, No. 6, 832–843 (2013a).

    CAS  PubMed  Google Scholar 

  • Kim, K. C., Kim, P., Go, H. S., et al., “The critical period of valproate exposure to induce autistic symptoms in Sprague–Dawley rats,” Toxicol. Lett., 201, No. 2, 137–142 (2011).

    CAS  PubMed  Google Scholar 

  • Kim, P., Park, J. H., Kwon, K. J., et al., “Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid,” Food Chem. Toxicol., 51, 288–296 (2013b).

    CAS  PubMed  Google Scholar 

  • Kudryavtseva, N. N., “Experience of defeat decreases the behavioural reactivity to conspecifics in the partition test,” Behav. Proc., 32, No. 3, 297–304 (1994).

    CAS  Google Scholar 

  • Lavrov, N. V. and Shabanov, P. D., “Autistic spectrum disorders: etiology, treatment, and experimental approaches to modeling,” Obzory Klin. Farmakol. Lek. Ter., 16, No. 1, 21–27 (2018).

    Google Scholar 

  • Li, Y., Zhou, Y., Peng, L., and Zhao, Y., “Reduced protein expressions of cytomembrane GABAARβ3 at different postnatal developmental stages of rats exposed prenatally to valproic acid,” Brain Res., 1671, 33–42 (2017).

    CAS  PubMed  Google Scholar 

  • Liang, M., Zhong, J., Liu, H., et al., “Pairmate-dependent pup retrieval as parental behavior in male mice,” Front. Neurosci., 8, 186, 1–10 (2014).

    Google Scholar 

  • Liu, H. X., Lopatina, O., Higashida, C., et al., “Displays of paternal mouse pup retrieval following communicative interaction with maternal mates,” Nat. Commun., 4, 1346–1348 (2013).

    PubMed  PubMed Central  Google Scholar 

  • Loomes, R., Hull, L., and Mandy, W. P. L., “What is the male-to-female ratio in autism spectrum disorder? A systematic review and meta-analysis,” J. Am. Acad. Child. Adolesc. Psychiatry, 56, No. 6, 466–474 (2017).

    PubMed  Google Scholar 

  • Lopatina, O. L., Furuhara, K., Ishihara, K., et al., “Communication impairment in ultrasonic vocal repertoire during the suckling period of Cd157 knockout mice: Transient improvement by oxytocin,” Front. Neurosci., 17, No. 11, 266 (2017).

    Google Scholar 

  • Lopatina, O., Yoshihara, T., Nishimura, T., et al., “Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson’s disease,” Front. Behav. Neurosci., 22, No. 8, 133 (2014).

    Google Scholar 

  • Lushchekina, E. A. and Strelets, V. B., “ Autistic spectrum disorders. Review of current experimental research,” Zh. Vyssh. Nerv. Deyat., 64, No. 6, 585–599 (2014).

    Google Scholar 

  • MacFabe, D. F., Cain, D. P., Rodriguez-Capote, K., et al., “Neurobiological effects of intraventricular propionic acid in rats: Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders,” Behav. Brain Res., 176, No. 1, 149–169 (2007).

    CAS  PubMed  Google Scholar 

  • MacFabe, D. F., Cain, N. E., Boon, F., et al., “Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder,” Behav. Brain Res., 217, No. 1, 47–54 (2011).

    CAS  PubMed  Google Scholar 

  • MacFabe, D. F., Thomas, R. H., Foley, K. A., et al., “Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: Further development of a potential model of autism spectrum disorders,” J. Neurochem., 113, No. 2, 515–529 (2010).

    PubMed  Google Scholar 

  • Main, S. L. and Kulesza, R. J., “Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia,” Neuroscience, 340, 34–47 (2017).

    CAS  Google Scholar 

  • Maraz, A., Hende, B., Urban, R., and Demetrovics, Z., “Pathological grooming: Evidence for a single factor behind trichotillomania, skin picking and nail biting,” PLoS One, 12, No. 9, 1–13 (2017).

    Google Scholar 

  • Markram, K., Rinaldi, T., Mendola, D., et al., “Abnormal fear conditioning and amygdala processing in an animal model of autism,” Neuropsychopharmacology, 33, No. 4, 901–912 (2008).

    PubMed  Google Scholar 

  • Mehta, M. V., Gandal, M. J., and Siegel, S. J., “mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism,” PLoS One, 6, 10, 1–6 (2011).

    Google Scholar 

  • Merten, S., Von Hoier, S., Pfeifle, C., and Tautz, D., “A role for ultrasonic vocalisation in social communication and divergence of natural populations of the house mouse (Mus musculus domesticus),” PLoS One, 9, 5, 1–18 (2014).

    Google Scholar 

  • Mineur, Y. S., Huynh, L. X., and Crusio, W. E., “Social behavior deficits in the Fmr1 mutant mouse,” Behav. Brain Res., 168, No. 1, 172–175 (2006).

    CAS  PubMed  Google Scholar 

  • Miyazaki, S., Hiraoka, Y., Hidema, S., and Nishimori, K., “Prenatal minocycline treatment alters synaptic protein expression, and rescues reduced mother call rate in oxytocin receptor-knockout mice,” Biochem. Biophys. Res. Commun, 472, No. 2, 319–323 (2016).

    CAS  PubMed  Google Scholar 

  • Moore, S. J., Turnpenny, P. D., Quinn, A., et al., “A clinical study of 57 children with fetal anticonvulsant syndromes,” J. Med. Genet., 37, No. 7, 489–497 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morland, C., Frøland, A.-S., Pettersen, M. N., et al., “Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA accumulation and lethargy in a model of propionic acidemia,” Biochem. J., 475, No. 4, 749–758 (2018).

    CAS  PubMed  Google Scholar 

  • Moy, S. S., Nadler, J. J., Young, N. B., et al., “Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains,” Behav. Brain Res., 176, No. 1, 4–20 (2007).

    PubMed  Google Scholar 

  • Munesue, T., Yokoyama, S., Nakamura, K., et al., “Two genetic variants of CD38 in subjects with autism spectrum disorder and controls,” Neurosci. Res., 67, No. 2, 181–191 (2010).

    CAS  PubMed  Google Scholar 

  • Nolan, S. O., Reynolds, C. D., Smith, G. D., et al., “Deletion of Fmr1 results in sex-specific changes in behavior,” Brain Behav., 7, 10, 1–13 (2017).

    Google Scholar 

  • Oddi, D., Subashi, E., Middei, S., et al., “Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome,” Neuropsychopharmacology, 40, No. 5, 1113–1122 (2015).

    PubMed  PubMed Central  Google Scholar 

  • Pelch, K. E., Bolden, A. L., and Kwiatkowski, C. F., “Environmental chemicals and autism: A scoping review of the human and animal research,” Environ. Health Perspect., 127, No. 4, 1–12 (2019).

    Google Scholar 

  • Pertsov, S. S., Koplik, E. V., Sakharov, et al., “Information-containing ultrasound interactions in rats,” Ros. Med. Biol. Vestn., No. 2, 109–118 (2012).

  • Pichugina, Yu. A., Arapiev, Yu. U., Lopatina, O. L., et al., “Analysis of the potentials of current methods for the diagnosis of autistic spectrum disorders,” Nevrol. Vestn., No. 1, 44–53 (2018).

  • Pietropaolo, S., Guilleminot, A., Martin, B., et al., “Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice,” PLoS One, 6, 2, 1–11 (2011).

    Google Scholar 

  • Pobbe, L., Pearson, B. L., Defensor, E. B., et al., Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors,” Horm. Behav., 61, No. 3, 436–444 (2012).

    CAS  PubMed  Google Scholar 

  • Qin, M., Huang, T., Kader, M., et al., “R-baclofen reverses a social behavior deficit and elevated protein synthesis in a mouse model of fragile X syndrome,” Int. J. Neuropsychopharmacol., 18, No. 9, 1–13 (2015).

    CAS  Google Scholar 

  • Robison, W. T., Myers, M. M., Hofer, M. A., et al., “Prairie vole pups show potentiated isolation-induced vocalizations following isolation from their mother, but not their father,” Dev. Psychobiol., 58, No. 6, 687–699 (2016).

    PubMed  Google Scholar 

  • Rodier, P. M., Ingram, J. L., Tisdale, B., and Croog, V. J., “Linking etiologies in humans and animal models: Studies of autism,” Reprod. Toxicol., 11, No. 2–3, 417–422 (1997).

    CAS  PubMed  Google Scholar 

  • Rodier, P. M., Ingram, J. L., Tisdale, B., et al., “Embryological origin for autism: Developmental anomalies of the cranial nerve motor nuclei,” J. Comp. Neurol., 370, No. 2, 247–261 (1996).

    CAS  PubMed  Google Scholar 

  • Sala, M., Braida, D., Donzelli, A., et al., “Mice heterozygous for the oxytocin receptor gene (Oxtr(+/–)) show impaired social behaviour but not increased aggression or cognitive inflexibility: Evidence of a selective haploinsufficiency gene effect,” J. Neuroendocrinol., 25, No. 2, 107–118 (2013).

    CAS  PubMed  Google Scholar 

  • Salmina, A. B., Lopatina, O., Ekimova, M. V., et al., “CD38/cyclic ADPribose system: A new player for oxytocin secretion and regulation of social behaviour,” J. Neuroendocrinol., 22, No. 5, 380–392 (2010).

    CAS  PubMed  Google Scholar 

  • Sauer, C., Montag, C., Worner, C., et al., “Effects of a common variant in the CD38 gene on social processing in an oxytocin challenge study: Possible links to autism,” Neuropsychopharmacology, 37, No. 6, 1474–1482 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Scattoni, M. L., Crawley, J., and Ricceri, L., “Ultrasonic vocalizations: a tool for behavioural phenotyping of mouse models of neurodevelopmental disorders,” Neurosci. Biobehav. Rev., 33, No. 4, 508–515 (2010).

    Google Scholar 

  • Schneider, T. and Przewłocki, R., “Behavioral alterations in rats prenatally to valproic acid: Animal model of autism,” Neuropsychopharmacology, 30, No. 1, 80–89 (2005).

    CAS  PubMed  Google Scholar 

  • Seffer, D., Schwarting, R. K. W., and Wöhr, M., “Pro-social ultrasonic communication in rats: Insights from playback studies,” J. Neurosci. Meth., 234, 73–81 (2014).

    Google Scholar 

  • Sethna, F., Feng, W., Ding, Q., et al., “Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model,” Nat. Commun., 8, 1–11 (2017).

    Google Scholar 

  • Shultz, S. R., Aziz, N. A. B., Yang, L., et al., “Intracerebroventricular injection of propionic acid, an enteric metabolite implicated in autism, induces social abnormalities that do not differ between seizure-prone (FAST) and seizure-resistant (SLOW) rats,” Behav. Brain Res., 278, 542–548 (2015).

    CAS  PubMed  Google Scholar 

  • Shultz, S. R., MacFabe, D. F., Ossenkopp, K. P., et al., “Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic end-product, impairs social behavior in the rat: Implications for an animal model of autism,” Neuropharmacology, 54, No. 6, 901–911 (2008).

    CAS  PubMed  Google Scholar 

  • Silverman, J. L., Tolu, S. S., Barkan, C. L., and Crawley, J. N., “Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP,” Neuropsychopharmacology, 35, No. 4, 976–989 (2009).

    PubMed  PubMed Central  Google Scholar 

  • Sinclair, D., Featherstone, R., Naschek, M., et al., “GABA-B agonist baclofen normalizes auditory-evoked neural oscillations and behavioral deficits in the Fmr1 knockout mouse model of fragile X syndrome,” eNeuro, 4, 1, 1–13 (2017).

    Google Scholar 

  • Spencer, C. M., Alekseyenko, O., Hamilton, S. M., et al., “Modifying behavioral phenotypes in Fmr1 KO mice: Genetic background differences reveal autistic-like responses,” Autism Res., 4, 1, 40–56 (2012).

    Google Scholar 

  • Tammimies, K., “Genetic mechanisms of regression in autism spectrum disorder,” Neurosci. Biobehav. Rev., 102, 208–220 (2019).

    CAS  PubMed  Google Scholar 

  • Tordjman, S., Somogyi, E., Coulon, N., et al., “Gene × environment interactions in autism spectrum disorders: Role of epigenetic mechanisms,” Front. Psychiatry, 5, 53, 1–17 (2014).

    Google Scholar 

  • Vasil’eva, L. N. and Bondar’, I. V., “Recognition of visual social stimuli: behavioral and neurophysiological mechanisms,” Zh. Vyssh. Nerv. Deyat., 68, No. 3, 273–291 (2018).

    Google Scholar 

  • Wahlsten, D., Metten, P., and Crabbe, J. C., “Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T/1 tf/tf has severely reduced hippocampal commissure and absent corpus callosum,” Brain Res., 971, No. 1, 47–54 (2003).

    CAS  PubMed  Google Scholar 

  • Wang, L., Cai, Y., and Fan, X., “Metformin administration during early postnatal life rescues autistic-like behaviors in the BTBR T+Itpr3tf/J mouse model of autism,” Front. Behav. Neurosci., 12, No. 290, 1–10 (2018).

    Google Scholar 

  • Wegiel Jerzy, Flory, M., Kuchna, I., et al., “Stereological study of the neuronal number and volume of 38 brain subdivisions of subjects diagnosed with autism reveals significant alterations restricted to the striatum, amygdala and cerebellum,” Acta Neuropathol. Commun., 2, 141, 1–18 (2014).

    Google Scholar 

  • Willner, P., “Animal models of depression: an overview,” Pharmacol. Ther., 45, No. 3, 425–455 (1990).

    CAS  PubMed  Google Scholar 

  • Winslow, J. T. and Insel, T. R., “The social deficits of the oxytocin knockout mouse,” Neuropeptides, 36, No. 2–3, 221–229 (2002).

    CAS  PubMed  Google Scholar 

  • Winslow, J. T., Young, L. J., Matzuk, M. M., et al., “Infant vocalization, adult aggression, and fear behavior of an oxytocin null mutant mouse,” Horm. Behav., 37, No. 2, 145–155 (2002).

    Google Scholar 

  • Wu, H. F., Chen, P. S., Hsu, Y. T., et al., “D-Cycloserine ameliorates autism-like deficits by removing GluA2-containing AMPA receptors in a valproic acid-induced rat model,” Mol. Neurobiol., 55, No. 6, 4811–4824 (2018).

    CAS  PubMed  Google Scholar 

  • Wu, H., Wang, X., Gao, J., et al., “Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism,” Life Sci., 173, 43–54 (2017).

    CAS  PubMed  Google Scholar 

  • Yamaguchi, H., Hara, Y., Ago, Y., et al., “Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice,” Behav. Brain Res., 333, 67–73 (2017).

    CAS  PubMed  Google Scholar 

  • Yang, M., Silverman, J. L., and Crawley, J. N., “Automated three-chambered social approach task for mice,” Curr. Protoc. Neurosci., Chapter 8, Unit 8.26, 1–23 (2016).

  • Zala, S. M., Reitschmidt, D., Noll, A., et al., “Sex-dependent modulation of ultrasonic vocalizations in house mice (Mus musculus musculus),” PLoS One, 12, No. 12, 1–15 (2017).

    Google Scholar 

  • Zhang, J., Liu, L. M., and Ni, J. F., “Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats,” Neuropsychiatr. Dis. Treat., 13, 835–842 (2017).

    PubMed  PubMed Central  Google Scholar 

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Correspondence to A. A. Semenova.

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Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 70, No. 2, pp. 147–162, March–April, 2020.

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Semenova, A.A., Lopatina, O.L. & Salmina, A.B. Models of Autism and Methods for Assessing Autistic-Like Behavior in Animals. Neurosci Behav Physi 50, 1024–1034 (2020). https://doi.org/10.1007/s11055-020-01002-0

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  • DOI: https://doi.org/10.1007/s11055-020-01002-0

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