Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.

1st Faculty of Medicine Charles University Katerinska 32 12108 Prague 2 Czech Republic

Faculty of Science Charles University Albertov 6 12800 Prague 2 Czech Republic

Laboratory of the Neurophysiology of the Memory Institute of Physiology of the Czech Academy of Sciences Videnska 1083 14220 Prague 4 Czech Republic

National Institute of Mental Health Topolova 748 25067 Klecany Czech Republic

Zobrazit více v PubMed

Brown A.S. Epidemiologic Studies of Exposure to Prenatal Infection and Risk of Schizophrenia and Autism. Dev. Neurobiol. 2012;72:1272–1276. doi: 10.1002/dneu.22024. PubMed DOI PMC

Buka S.L., Tsuang M.T., Torrey E.F., Klebanoff M.A., Wagner R.L., Yolken R.H. Maternal Cytokine Levels during Pregnancy and Adult Psychosis. Brain. Behav. Immun. 2001;15:411–420. doi: 10.1006/brbi.2001.0644. PubMed DOI

Schmitt A., Malchow B., Hasan A., Falkai P. The Impact of Environmental Factors in Severe Psychiatric Disorders. Front. Neurosci. 2014;8:1–10. doi: 10.3389/fnins.2014.00019. PubMed DOI PMC

Tordjman S., Drapier D., Bonnot O., Graignic R., Fortes S., Cohen D., Millet B., Laurent C., Roubertoux P.L. Animal Models Relevant to Schizophrenia and Autism: Validity and Limitations. Behav. Genet. 2007;37:61–78. doi: 10.1007/s10519-006-9120-5. PubMed DOI

Volkmar F.R., Lord C., Bailey A., Schultz R.T., Klin A. Autism and Pervasive Developmental Disorders. J. Child Psychol. Psychiatry. 2004;45:135–170. doi: 10.1046/j.0021-9630.2003.00317.x. PubMed DOI

American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders (DSM-5®®) 5th ed. American Psychiatric Association; Arlington, VA, USA: 2013.

Owen M.J., Sawa A., Mortensen P.B. Schizophrenia. Lancet. 2016;388:86–97. doi: 10.1016/S0140-6736(15)01121-6. PubMed DOI PMC

Kodish I., McClellan J.M. Dulcan’s Textbook of Child and Adolescent Psychiatry. 2nd ed. American Psychiatric Publishing, Inc.; Arlington, VA, USA: 2016. Early onset schizophrenia; pp. 389–408.

Parnas J., Bovet P., Zahavi D. Schizophrenic Autism: Clinical Phenomenology and Pathogenetic Implications. World Psychiatry. 2002;1:131–136. PubMed PMC

Pina-Camacho L., Parellada M., Kyriakopoulos M. Autism Spectrum Disorder and Schizophrenia: Boundaries and Uncertainties. BJPsych Adv. 2016;22:316–324. doi: 10.1192/apt.bp.115.014720. DOI

Rimol L.M., Hartberg C.B., Nesvåg R., Fennema-Notestine C., Hagler D.J., Pung C.J., Jennings R.G., Haukvik U.K., Lange E., Nakstad P.H., et al. Cortical Thickness and Subcortical Volumes in Schizophrenia and Bipolar Disorder. Biol. Psychiatry. 2010;68:41–50. doi: 10.1016/j.biopsych.2010.03.036. PubMed DOI

Amaral D.G., Schumann C.M., Nordahl C.W. Neuroanatomy of Autism. Trends Neurosci. 2008;31:137–145. doi: 10.1016/j.tins.2007.12.005. PubMed DOI

Courchesne E., Carper R., Akshoomoff N. Evidence of Brain Overgrowth in the First Year of Life in Autism. JAMA. 2003;290:337–344. doi: 10.1001/jama.290.3.337. PubMed DOI

Hadjikhani N., Joseph R.M., Snyder J., Tager-Flusberg H. Anatomical Differences in the Mirror Neuron System and Social Cognition Network in Autism. Cereb. Cortex. 2006;16:1276–1282. doi: 10.1093/cercor/bhj069. PubMed DOI

Hardan A.Y., Muddasani S., Vemulapalli M., Keshavan M.S., Minshew N.J. An MRI Study of Increased Cortical Thickness in Autism. Am. J. Psychiatry. 2006;163:1290–1292. doi: 10.1176/ajp.2006.163.7.1290. PubMed DOI PMC

Schumann C.M., Hamstra J., Goodlin-Jones B.L., Lotspeich L.J., Kwon H., Buonocore M.H., Lammers C.R., Reiss A.L., Amaral D.G. The Amygdala Is Enlarged in Children but Not Adolescents with Autism; the Hippocampus Is Enlarged at All Ages. J. Neurosci. 2004;24:6392–6401. doi: 10.1523/JNEUROSCI.1297-04.2004. PubMed DOI PMC

Gonzalez-Burgos G., Cho R.Y., Lewis D.A. Alterations in Cortical Network Oscillations and Parvalbumin Neurons in Schizophrenia. Biol. Psychiatry. 2015;77:1031–1040. doi: 10.1016/j.biopsych.2015.03.010. PubMed DOI PMC

Hashemi E., Ariza J., Rogers H., Noctor S.C., Martínez-Cerdeño V. The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Prefrontal Cortex in Autism. Cereb. Cortex. 2017;27:1931–1943. doi: 10.1093/cercor/bhx063. PubMed DOI PMC

Lawrence Y.A., Kemper T.L., Bauman M.L., Blatt G.J. Parvalbumin-, Calbindin-, and Calretinin-Immunoreactive Hippocampal Interneuron Density in Autism. Acta Neurol. Scand. 2010;121:99–108. doi: 10.1111/j.1600-0404.2009.01234.x. PubMed DOI

Stedehouder J., Kushner S.A. Myelination of Parvalbumin Interneurons: A Parsimonious Locus of Pathophysiological Convergence in Schizophrenia. Mol. Psychiatry. 2017;22:4–12. doi: 10.1038/mp.2016.147. PubMed DOI PMC

Krajcovic B., Fajnerova I., Horacek J., Kelemen E., Kubik S., Svoboda J., Stuchlik A. Neural and Neuronal Discoordination in Schizophrenia: From Ensembles through Networks to Symptoms. Acta Physiol. 2019;226:e13282. doi: 10.1111/apha.13282. PubMed DOI

Nakamura T., Matsumoto J., Takamura Y., Ishii Y., Sasahara M., Ono T., Nishijo H. Relationships among Parvalbumin-Immunoreactive Neuron Density, Phase-Locked Gamma Oscillations, and Autistic/Schizophrenic Symptoms in PDGFR-β Knock-out and Control Mice. PLoS ONE. 2015;10:e0119258. doi: 10.1371/journal.pone.0119258. PubMed DOI PMC

Nguyen R., Morrissey M.D., Mahadevan V., Cajanding J.D., Woodin M.A., Yeomans J.S., Takehara-Nishiuchi K., Kim J.C. Parvalbumin and GAD65 Interneuron Inhibition in the Ventral Hippocampus Induces Distinct Behavioral Deficits Relevant to Schizophrenia. J. Neurosci. 2014;34:14948–14960. doi: 10.1523/JNEUROSCI.2204-14.2014. PubMed DOI PMC

Berkowicz S.R., Featherby T.J., Qu Z., Giousoh A., Borg N.A., Heng J.I., Whisstock J.C., Bird P.I. Brinp1 −/− Mice Exhibit Autism-like Behaviour, Altered Memory, Hyperactivity and Increased Parvalbumin-Positive Cortical Interneuron Density. Mol. Autism. 2016;7:22. doi: 10.1186/s13229-016-0079-7. PubMed DOI PMC

Saunders J.A., Tatard-Leitman V.M., Suh J., Billingslea E.N., Roberts T.P., Siegel S.J. Knockout of NMDA Receptors in Parvalbumin Interneurons Recreates Autism-like Phenotypes. Autism Res. 2013;6:69–77. doi: 10.1002/aur.1264. PubMed DOI PMC

Wöhr M., Orduz D., Gregory P., Moreno H., Khan U., Vörckel K.J., Wolfer D.P., Welzl H., Gall D., Schiffmann S.N., et al. Lack of Parvalbumin in Mice Leads to Behavioral Deficits Relevant to All Human Autism Core Symptoms and Related Neural Morphofunctional Abnormalities. Transl. Psychiatry. 2015;5:e525. doi: 10.1038/tp.2015.19. PubMed DOI PMC

Baharnoori M., Bhardwaj S.K., Srivastava L.K. Neonatal Behavioral Changes in Rats with Gestational Exposure to Lipopolysaccharide: A Prenatal Infection Model for Developmental Neuropsychiatric Disorders. Schizophr. Bull. 2012;38:444–456. doi: 10.1093/schbul/sbq098. PubMed DOI PMC

Basta-Kaim A., Fijał K., Budziszewska B., Regulska M., Leśkiewicz M., Kubera M., Gołembiowska K., Lasoń W., Wędzony K. Prenatal Lipopolysaccharide Treatment Enhances MK-801-Induced Psychotomimetic Effects in Rats. Pharmacol. Biochem. Behav. 2011;98:241–249. doi: 10.1016/j.pbb.2010.12.026. PubMed DOI

Fatemi S.H., Reutiman T.J., Folsom T.D., Huang H., Oishi K., Mori S., Smee D.F., Pearce D.A., Winter C., Sohr R., et al. Maternal Infection Leads to Abnormal Gene Regulation and Brain Atrophy in Mouse Offspring: Implications for Genesis of Neurodevelopmental Disorders. Schizophr. Res. 2008;99:56–70. doi: 10.1016/j.schres.2007.11.018. PubMed DOI PMC

Meyer U. Prenatal Poly(I:C) Exposure and Other Developmental Immune Activation Models in Rodent Systems. Biol. Psychiatry. 2014;75:307–315. doi: 10.1016/j.biopsych.2013.07.011. PubMed DOI

Nakamura J.P., Gillespie B., Gibbons A., Jaehne E.J., Du X., Chan A., Schroeder A., van den Buuse M., Sundram S., Hill R.A. Maternal Immune Activation Targeted to a Window of Parvalbumin Interneuron Development Improves Spatial Working Memory: Implications for Autism. Brain. Behav. Immun. 2021;91:339–349. doi: 10.1016/j.bbi.2020.10.012. PubMed DOI

Patterson P.H. Maternal Infection and Immune Involvement in Autism. Trends Mol. Med. 2011;17:389–394. doi: 10.1016/j.molmed.2011.03.001. PubMed DOI PMC

Batinić B., Santrač A., Divović B., Timić T., Stanković T., Obradović A.L., Joksimović S., Savić M.M. Lipopolysaccharide Exposure during Late Embryogenesis Results in Diminished Locomotor Activity and Amphetamine Response in Females and Spatial Cognition Impairment in Males in Adult, but Not Adolescent Rat Offspring. Behav. Brain Res. 2016;299:72–80. doi: 10.1016/j.bbr.2015.11.025. PubMed DOI

Henry C.J., Huang Y., Wynne A.M., Godbout J.P. Peripheral Lipopolysaccharide (LPS) Challenge Promotes Microglial Hyperactivity in Aged Mice That Is Associated with Exaggerated Induction of Both pro-Inflammatory IL-1β and Anti-Inflammatory IL-10 Cytokines. Brain Behav. Immun. 2009;23:309–317. doi: 10.1016/j.bbi.2008.09.002. PubMed DOI PMC

Solati J., Kleehaupt E., Kratz O., Moll G.H., Golub Y. Inverse Effects of Lipopolysaccharides on Anxiety in Pregnant Mice and Their Offspring. Physiol. Behav. 2015;139:369–374. doi: 10.1016/j.physbeh.2014.10.016. PubMed DOI

Van Amersfoort E.S., Van Berkel T.J.C., Kuiper J. Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock. Clin. Microbiol. Rev. 2003;16:379–414. doi: 10.1128/CMR.16.3.379-414.2003. PubMed DOI PMC

Cai Z., Pan Z.-L., Pang Y., Evans O.B., Rhodes P.G. Cytokine Induction in Fetal Rat Brains and Brain Injury in Neonatal Rats after Maternal Lipopolysaccharide Administration. Pediatr. Res. 2000;47:64. doi: 10.1203/00006450-200001000-00013. PubMed DOI

Romero E., Guaza C., Castellano B., Borrell J. Ontogeny of Sensorimotor Gating and Immune Impairment Induced by Prenatal Immune Challenge in Rats: Implications for the Etiopathology of Schizophrenia. Mol. Psychiatry. 2010;15:372–383. doi: 10.1038/mp.2008.44. PubMed DOI

Boksa P. Effects of Prenatal Infection on Brain Development and Behavior: A Review of Findings from Animal Models. Brain Behav. Immun. 2010;24:881–897. doi: 10.1016/j.bbi.2010.03.005. PubMed DOI

McPartland J.C., Law K., Dawson G. Encyclopedia of Mental Health. Elsevier; Amsterdam, The Netherlands: 2016. Autism Spectrum Disorder; pp. 124–130.

Ochoa S., Usall J., Cobo J., Labad X., Kulkarni J. Gender Differences in Schizophrenia and First-Episode Psychosis: A Comprehensive Literature Review. Schizophr. Res. Treat. 2012;2012:1–9. doi: 10.1155/2012/916198. PubMed DOI PMC

Werling D.M., Geschwind D.H. Sex Differences in Autism Spectrum Disorders. Curr. Opin. Neurol. 2013;26:146–153. doi: 10.1097/WCO.0b013e32835ee548. PubMed DOI PMC

Potasiewicz A., Holuj M., Piotrowska D., Zajda K., Wojcik M., Popik P., Nikiforuk A. Evaluation of Ultrasonic Vocalizations in a Neurodevelopmental Model of Schizophrenia during the Early Life Stages of Rats. Neuropharmacology. 2019;146:28–38. doi: 10.1016/j.neuropharm.2018.11.023. PubMed DOI

Basta-Kaim A., Fijał K., Ślusarczyk J., Trojan E., Głombik K., Budziszewska B., Leśkiewicz M., Regulska M., Kubera M., Lasoń W., et al. Prenatal Administration of Lipopolysaccharide Induces Sex-Dependent Changes in Glutamic Acid Decarboxylase and Parvalbumin in the Adult Rat Brain. Neuroscience. 2015;287:78–92. doi: 10.1016/j.neuroscience.2014.12.013. PubMed DOI

Wischhof L., Irrsack E., Osorio C., Koch M. Prenatal LPS-Exposure—A Neurodevelopmental Rat Model of Schizophrenia—Differentially Affects Cognitive Functions, Myelination and Parvalbumin Expression in Male and Female Offspring. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2015;57:17–30. doi: 10.1016/j.pnpbp.2014.10.004. PubMed DOI

Frankle W.G., Cho R.Y., Prasad K.M., Mason N.S., Paris J., Himes M.L., Walker C., Lewis D.A., Narendran R. In Vivo Measurement of GABA Transmission in Healthy Subjects and Schizophrenia Patients. Am. J. Psychiatry. 2015;172:1148–1159. doi: 10.1176/appi.ajp.2015.14081031. PubMed DOI PMC

Curley A.A., Arion D., Volk D.W., Asafu-Adjei J.K., Sampson A.R., Fish K.N., Lewis D.A. Cortical Deficits of Glutamic Acid Decarboxylase 67 Expression in Schizophrenia: Clinical, Protein, and Cell Type-Specific Features. Am. J. Psychiatry. 2011;168:921–929. doi: 10.1176/appi.ajp.2011.11010052. PubMed DOI PMC

Glausier J.R., Fish K.N., Lewis D.A. Altered Parvalbumin Basket Cell Inputs in the Dorsolateral Prefrontal Cortex of Schizophrenia Subjects. Mol. Psychiatry. 2014;19:30–36. doi: 10.1038/mp.2013.152. PubMed DOI PMC

Konradi C., Yang C.K., Zimmerman E.I., Lohmann K.M., Gresch P., Pantazopoulos H., Berretta S., Heckers S. Hippocampal Interneurons are Abnormal in Schizophrenia. Schizophr. Res. 2011;131:165–173. doi: 10.1016/j.schres.2011.06.007. PubMed DOI PMC

Gonzalez-Burgos G., Hashimoto T., Lewis D.A. Alterations of Cortical GABA Neurons and Network Oscillations in Schizophrenia. Curr. Psychiatry Rep. 2010;12:335–344. doi: 10.1007/s11920-010-0124-8. PubMed DOI PMC

Lewis D.A., Curley A.A., Glausier J.R., Volk D.W. Cortical Parvalbumin Interneurons and Cognitive Dysfunction in Schizophrenia. Trends Neurosci. 2012;35:57–67. doi: 10.1016/j.tins.2011.10.004. PubMed DOI PMC

Kirsten T.B., Taricano M., Maiorka P.C., Palermo-Neto J., Bernardi M.M. Prenatal Lipopolysaccharide Reduces Social Behavior in Male Offspring. Neuroimmunomodulation. 2010;17:240–251. doi: 10.1159/000290040. PubMed DOI

Chen Z., Jalabi W., Shpargel K.B., Farabaugh K.T., Dutta R., Yin X., Kidd G.J., Bergmann C.C., Stohlman S.A., Trapp B.D. Lipopolysaccharide-Induced Microglial Activation and Neuroprotection against Experimental Brain Injury Is Independent of Hematogenous TLR4. J. Neurosci. 2012;32:11706–11715. doi: 10.1523/JNEUROSCI.0730-12.2012. PubMed DOI PMC

Pang Y., Dai X., Roller A., Carter K., Paul I., Bhatt A.J., Lin R.C.S., Fan L.-W. Early Postnatal Lipopolysaccharide Exposure Leads to Enhanced Neurogenesis and Impaired Communicative Functions in Rats. PLoS ONE. 2016;11:e0164403. doi: 10.1371/journal.pone.0164403. PubMed DOI PMC

Courchesne E., Karns C.M., Davis H.R., Ziccardi R., Carper R.A., Tigue Z.D., Chisum H.J., Moses P., Pierce K., Lord C., et al. Unusual Brain Growth Patterns in Early Life in Patients with Autistic Disorder: An MRI Study. Neurology. 2001;57:245–254. doi: 10.1212/WNL.57.2.245. PubMed DOI

Dawson G., Munson J., Webb S.J., Nalty T., Abbott R., Toth K. Rate of Head Growth Decelerates and Symptoms Worsen in the Second Year of Life in Autism. Biol. Psychiatry. 2007;61:458–464. doi: 10.1016/j.biopsych.2006.07.016. PubMed DOI PMC

Dementieva Y.A., Vance D.D., Donnelly S.L., Elston L.A., Wolpert C.M., Ravan S.A., DeLong G.R., Abramson R.K., Wright H.H., Cuccaro M.L. Accelerated Head Growth in Early Development of Individuals with Autism. Pediatr. Neurol. 2005;32:102–108. doi: 10.1016/j.pediatrneurol.2004.08.005. PubMed DOI

Barkataki I., Kumari V., Das M., Taylor P., Sharma T. Volumetric Structural Brain Abnormalities in Men with Schizophrenia or Antisocial Personality Disorder. Behav. Brain Res. 2006;169:239–247. doi: 10.1016/j.bbr.2006.01.009. PubMed DOI

Foley K.A., MacFabe D.F., Vaz A., Ossenkopp K., Kavaliers M. 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. 2014;39:68–78. doi: 10.1016/j.ijdevneu.2014.04.001. PubMed DOI

Vojtechova I., Petrasek T., Maleninska K., Brozka H., Tejkalova H., Horacek J., Stuchlik A., Vales K. Neonatal Immune Activation by Lipopolysaccharide Causes Inadequate Emotional Responses to Novel Situations but No Changes in Anxiety or Cognitive Behavior in Wistar Rats. Behav. Brain Res. 2018;349:42–53. doi: 10.1016/j.bbr.2018.05.001. PubMed DOI

DeLisi L.E. Speech Disorder in Schizophrenia: Review of the Literature and Exploration of Its Relation to the Uniquely Human Capacity for Language. Schizophr. Bull. 2001;27:481–496. doi: 10.1093/oxfordjournals.schbul.a006889. PubMed DOI

McKenna P.J., Oh T.M., Oh T. Schizophrenic Speech: Making Sense of Bathroots and Ponds That Fall in Doorways. Cambridge University Press; Cambridge, UK: 2005.

Hogg S. A Review of the Validity and Variability of the Elevated Plus-Maze as an Animal Model of Anxiety. Pharmacol. Biochem. Behav. 1996;54:21–30. doi: 10.1016/0091-3057(95)02126-4. PubMed DOI

Ramos A. Animal Models of Anxiety: Do I Need Multiple Tests? Trends Pharmacol. Sci. 2008;29:493–498. doi: 10.1016/j.tips.2008.07.005. PubMed DOI

Depino A.M. Early Prenatal Exposure to LPS Results in Anxiety- and Depression-Related Behaviors in Adulthood. Neuroscience. 2015;299:56–65. doi: 10.1016/j.neuroscience.2015.04.065. PubMed DOI

Lin Y.-L., Lin S.-Y., Wang S. Prenatal Lipopolysaccharide Exposure Increases Anxiety-like Behaviors and Enhances Stress-Induced Corticosterone Responses in Adult Rats. Brain Behav. Immun. 2012;26:459–468. doi: 10.1016/j.bbi.2011.12.003. PubMed DOI

Foley K.A., Ossenkopp K.-P., Kavaliers M., MacFabe D.F. Pre- and Neonatal Exposure to Lipopolysaccharide or the Enteric Metabolite, Propionic Acid, Alters Development and Behavior in Adolescent Rats in a Sexually Dimorphic Manner. PLoS ONE. 2014;9:e87072. doi: 10.1371/journal.pone.0087072. PubMed DOI PMC

Lysaker P.H., Salyers M.P. Anxiety Symptoms in Schizophrenia Spectrum Disorders: Associations with Social Function, Positive and Negative Symptoms, Hope and Trauma History. Acta Psychiatr. Scand. 2007;116:290–298. doi: 10.1111/j.1600-0447.2007.01067.x. PubMed DOI

White S.W., Oswald D., Ollendick T., Scahill L. Anxiety in Children and Adolescents with Autism Spectrum Disorders. Clin. Psychol. Rev. 2009;29:216–229. doi: 10.1016/j.cpr.2009.01.003. PubMed DOI PMC

Bubenikova-Valesova V., Horacek J., Vrajova M., Hoschl C. Models of Schizophrenia in Humans and Animals Based on Inhibition of NMDA Receptors. Neurosci. Biobehav. Rev. 2008;32:1014–1023. doi: 10.1016/j.neubiorev.2008.03.012. PubMed DOI

de Oliveira L., Fraga D.B., De Luca R.D., Canever L., Ghedim F.V., Matos M.P.P., Streck E.L., Quevedo J., Zugno A.I. Behavioral Changes and Mitochondrial Dysfunction in a Rat Model of Schizophrenia Induced by Ketamine. Metab. Brain Dis. 2011;26:69–77. doi: 10.1007/s11011-011-9234-1. PubMed DOI

Shirai Y., Fujita Y., Hashimoto K. Effects of the Antioxidant Sulforaphane on Hyperlocomotion and Prepulse Inhibition Deficits in Mice after Phencyclidine Administration. Clin. Psychopharmacol. Neurosci. 2012;10:94–98. doi: 10.9758/cpn.2012.10.2.94. PubMed DOI PMC

Sun T., Hu G., Li M. Repeated Antipsychotic Treatment Progressively Potentiates Inhibition on Phencyclidine-Induced Hyperlocomotion, but Attenuates Inhibition on Amphetamine-Induced Hyperlocomotion: Relevance to Animal Models of Antipsychotic Drugs. Eur. J. Pharmacol. 2009;602:334–342. doi: 10.1016/j.ejphar.2008.11.036. PubMed DOI

Vojtechova I., Petrasek T., Hatalova H., Pistikova A., Vales K., Stuchlik A. Dizocilpine (MK-801) Impairs Learning in the Active Place Avoidance Task but Has No Effect on the Performance during Task/Context Alternation. Behav. Brain Res. 2016;305:247–257. doi: 10.1016/j.bbr.2016.03.020. PubMed DOI

Tejkalova H., Jelinek F., Klaschka J., Stastny F. Effect of perinatal inflammatory reaction on the induction of psychotic-like behaviour: Experimental study. Psychiatrie. 2007;11:12–15.

Stigger F., Lovatel G., Marques M., Bertoldi K., Moysés F., Elsner V., Siqueira I.R., Achaval M., Marcuzzo S. Inflammatory Response and Oxidative Stress in Developing Rat Brain and Its Consequences on Motor Behavior Following Maternal Administration of LPS and Perinatal Anoxia. Int. J. Dev. Neurosci. 2013;31:820–827. doi: 10.1016/j.ijdevneu.2013.10.003. PubMed DOI

Foussias G., Remington G. Negative Symptoms in Schizophrenia: Avolition and Occam’s Razor. Schizophr. Bull. 2010;36:359–369. doi: 10.1093/schbul/sbn094. PubMed DOI PMC

Foley K.A., MacFabe D.F., Kavaliers M., Ossenkopp K.-P. Sexually Dimorphic Effects of Prenatal Exposure to Lipopolysaccharide, and Prenatal and Postnatal Exposure to Propionic Acid, on Acoustic Startle Response and Prepulse Inhibition in Adolescent Rats: Relevance to Autism Spectrum Disorders. Behav. Brain Res. 2015;278:244–256. doi: 10.1016/j.bbr.2014.09.032. PubMed DOI

Fortier M.-E., Luheshi G.N., Boksa P. Effects of Prenatal Infection on Prepulse Inhibition in the Rat Depend on the Nature of the Infectious Agent and the Stage of Pregnancy. Behav. Brain Res. 2007;181:270–277. doi: 10.1016/j.bbr.2007.04.016. PubMed DOI

Braff D.L., Geyer M.A., Light G.A., Sprock J., Perry W., Cadenhead K.S., Swerdlow N.R. Impact of Prepulse Characteristics on the Detection of Sensorimotor Gating Deficits in Schizophrenia. Schizophr. Res. 2001;49:171–178. doi: 10.1016/S0920-9964(00)00139-0. PubMed DOI

Geyer M.A., Krebs-Thomson K., Braff D.L., Swerdlow N.R. Pharmacological Studies of Prepulse Inhibition Models of Sensorimotor Gating Deficits in Schizophrenia: A Decade in Review. Psychopharmacology. 2001;156:117–154. doi: 10.1007/s002130100811. PubMed DOI

Kohl S., Heekeren K., Klosterkötter J., Kuhn J. Prepulse Inhibition in Psychiatric Disorders—Apart from Schizophrenia. J. Psychiatr. Res. 2013;47:445–452. doi: 10.1016/j.jpsychires.2012.11.018. PubMed DOI

Madsen G.F., Bilenberg N., Cantio C., Oranje B. Increased Prepulse Inhibition and Sensitization of the Startle Reflex in Autistic Children: Sensorimotor Gating in Autistic Children. Autism Res. 2014;7:94–103. doi: 10.1002/aur.1337. PubMed DOI

Perry W., Minassian A., Lopez B., Maron L., Lincoln A. Sensorimotor Gating Deficits in Adults with Autism. Biol. Psychiatry. 2007;61:482–486. doi: 10.1016/j.biopsych.2005.09.025. PubMed DOI

Kohl S., Wolters C., Gruendler T.O.J., Vogeley K., Klosterkötter J., Kuhn J. Prepulse Inhibition of the Acoustic Startle Reflex in High Functioning Autism. PLoS ONE. 2014;9:e92372. doi: 10.1371/journal.pone.0092372. PubMed DOI PMC

Meyer U., Feldon J., Dammann O. Schizophrenia and Autism: Both Shared and Disorder-Specific Pathogenesis via Perinatal Inflammation? Pediatr. Res. 2011;69:26R–33R. doi: 10.1203/PDR.0b013e318212c196. PubMed DOI PMC

Marcondes F.K., Bianchi F.J., Tanno A.P. Determination of the Estrous Cycle Phases of Rats: Some Helpful Considerations. Braz. J. Biol. 2002;62:609–614. doi: 10.1590/S1519-69842002000400008. PubMed DOI

Paxinos G., Watson C. The Rat Brain in Stereotaxic Coordinates. 6th ed. Academic Press; Boston, MA, USA: Elsevier; Amsterdam, The Netherlands: 2007.

Wallace C.S., Reitzenstein J., Withers G.S. Diminished Experience-Dependent Neuroanatomical Plasticity: Evidence for an Improved Biomarker of Subtle Neurotoxic Damage to the Developing Rat Brain. Environ. Health Perspect. 2003;111:1294–1298. doi: 10.1289/ehp.6088. PubMed DOI PMC

Yan E.B., Hellewell S.C., Bellander B.-M., Agyapomaa D.A., Morganti-Kossmann M.C. Post-Traumatic Hypoxia Exacerbates Neurological Deficit, Neuroinflammation and Cerebral Metabolism in Rats with Diffuse Traumatic Brain Injury. J. Neuroinflammation. 2011;8:147. doi: 10.1186/1742-2094-8-147. PubMed DOI PMC

Bures J., Fenton A.A., Kaminsky Y., Zinyuk L. Place Cells and Place Navigation. Proc. Natl. Acad. Sci. USA. 1997;94:343–350. doi: 10.1073/pnas.94.1.343. PubMed DOI PMC

Fenton A.A., Wesierska M., Kaminsky Y., Bures J. Both Here and There: Simultaneous Expression of Autonomous Spatial Memories in Rats. Proc. Natl. Acad. Sci. USA. 1998;95:11493–11498. doi: 10.1073/pnas.95.19.11493. PubMed DOI PMC

Stuchlík A., Petrásek T., Prokopová I., Holubová K., Hatalová H., Valeš K., Kubík Š., Dockery C., Wesierska M. Place Avoidance Tasks as Tools in the Behavioral Neuroscience of Learning and Memory. Physiol. Res. 2013;62:S1–S19. doi: 10.33549/physiolres.932635. PubMed DOI

Friard O., Gamba M. BORIS: A Free, Versatile Open-Source Event-Logging Software for Video/Audio Coding and Live Observations. Methods Ecol. Evol. 2016;7:1325–1330. doi: 10.1111/2041-210X.12584. DOI

Burke A.W., Broadhurst P.L. Behavioural Correlates of the Oestrous Cycle in the Rat. Nature. 1966;209:223–224. doi: 10.1038/209223a0. PubMed DOI

Feltenstein M.W., See R.E. Plasma Progesterone Levels and Cocaine-Seeking in Freely Cycling Female Rats across the Estrous Cycle. Drug Alcohol Depend. 2007;89:183–189. doi: 10.1016/j.drugalcdep.2006.12.017. PubMed DOI PMC

Rousset C.I., Kassem J., Aubert A., Planchenault D., Gressens P., Chalon S., Belzung C., Saliba E. Maternal Exposure to Lipopolysaccharide Leads to Transient Motor Dysfunction in Neonatal Rats. Dev. Neurosci. 2013;35:172–181. doi: 10.1159/000346579. PubMed DOI