A new two-hit animal model for schizophrenia research: Consequences on social behavior
Schizophrenia, a profoundly impactful neuropsychiatric disorder, has been the subject of extensive research using animal models. However, certain important aspects remain understudied, including assumed long-term consequences of psychotic episodes on negative symptoms development and progression. Ad...
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Elsevier
2025-12-01
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| Series: | IBRO Neuroscience Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667242125000788 |
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| author | Kristina Hakenova Anna Mikulecka Kristina Holubova Marketa Chvojkova Romana Slamberova Jana Jurcovicova Barbora Cechova Silvester Ponist Jiri Horacek Karel Vales |
| author_facet | Kristina Hakenova Anna Mikulecka Kristina Holubova Marketa Chvojkova Romana Slamberova Jana Jurcovicova Barbora Cechova Silvester Ponist Jiri Horacek Karel Vales |
| author_sort | Kristina Hakenova |
| collection | DOAJ |
| description | Schizophrenia, a profoundly impactful neuropsychiatric disorder, has been the subject of extensive research using animal models. However, certain important aspects remain understudied, including assumed long-term consequences of psychotic episodes on negative symptoms development and progression. Addressing these limitations, we proposed a novel animal model in male rats based on early postnatal immune activation triggered by lipopolysaccharide (LPS), serving as the predisposing factor (1st hit). As the 2nd hit, representing psychotic-like episodes, we implemented a multi-episodic co-treatment with dizocilpine (MK-801) and amphetamine (AMP), spanning multiple developmental periods. The animals were tested in two social behavioral assays in adolescence and adulthood to investigate whether a social deficit would arise. In addition, we evaluated the level of oxytocin (OT), a neuropeptide relevant to social behavior, in selected brain regions. In the social interaction test, when animals could freely interact in the open field and express their social behavioral profile entirely, social behavior decreased in adolescent experimental animals. In the social approach test in the Y maze, all animals, irrespective of treatment, preferred conspecific over an indifferent object and novel rat over a familiar rat. Further, the results revealed that the OT content in the hypothalamus increased with age. In the proposed model, social interaction in the open field was decreased in adolescent but not in adult rats, indicating that the pharmacological manipulations caused only transient age-dependent changes. The study was thus in certain aspects successful in creating a novel approach to model social deficit potentially relevant to schizophrenia; other findings require further investigation. |
| format | Article |
| id | doaj-art-baa9266017844fdc825225eeb99bf34e |
| institution | OA Journals |
| issn | 2667-2421 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | IBRO Neuroscience Reports |
| spelling | doaj-art-baa9266017844fdc825225eeb99bf34e2025-08-20T02:32:23ZengElsevierIBRO Neuroscience Reports2667-24212025-12-0119384910.1016/j.ibneur.2025.05.012A new two-hit animal model for schizophrenia research: Consequences on social behaviorKristina Hakenova0Anna Mikulecka1Kristina Holubova2Marketa Chvojkova3Romana Slamberova4Jana Jurcovicova5Barbora Cechova6Silvester Ponist7Jiri Horacek8Karel Vales9National Institute of Mental Health, Topolova 748, Klecany 250 67, Czech Republic; Charles University, Third Faculty of Medicine, Ruska 87, Prague 100 00, Czech RepublicInstitute of Physiology CAS, Videnska 1083, Prague 142 20, Czech RepublicNational Institute of Mental Health, Topolova 748, Klecany 250 67, Czech RepublicNational Institute of Mental Health, Topolova 748, Klecany 250 67, Czech Republic; Corresponding author.Charles University, Third Faculty of Medicine, Department of Physiology, Ke Karlovu 4, Prague 120 00, Czech RepublicCharles University, Third Faculty of Medicine, Department of Physiology, Ke Karlovu 4, Prague 120 00, Czech RepublicCharles University, Third Faculty of Medicine, Department of Physiology, Ke Karlovu 4, Prague 120 00, Czech RepublicCentre of Experimental Medicine SAS, Institute of Experimental Pharmacology & Toxicology, Dúbravská cesta 9, Bratislava 841 04, Slovak RepublicNational Institute of Mental Health, Topolova 748, Klecany 250 67, Czech RepublicNational Institute of Mental Health, Topolova 748, Klecany 250 67, Czech Republic; Charles University, Third Faculty of Medicine, Ruska 87, Prague 100 00, Czech RepublicSchizophrenia, a profoundly impactful neuropsychiatric disorder, has been the subject of extensive research using animal models. However, certain important aspects remain understudied, including assumed long-term consequences of psychotic episodes on negative symptoms development and progression. Addressing these limitations, we proposed a novel animal model in male rats based on early postnatal immune activation triggered by lipopolysaccharide (LPS), serving as the predisposing factor (1st hit). As the 2nd hit, representing psychotic-like episodes, we implemented a multi-episodic co-treatment with dizocilpine (MK-801) and amphetamine (AMP), spanning multiple developmental periods. The animals were tested in two social behavioral assays in adolescence and adulthood to investigate whether a social deficit would arise. In addition, we evaluated the level of oxytocin (OT), a neuropeptide relevant to social behavior, in selected brain regions. In the social interaction test, when animals could freely interact in the open field and express their social behavioral profile entirely, social behavior decreased in adolescent experimental animals. In the social approach test in the Y maze, all animals, irrespective of treatment, preferred conspecific over an indifferent object and novel rat over a familiar rat. Further, the results revealed that the OT content in the hypothalamus increased with age. In the proposed model, social interaction in the open field was decreased in adolescent but not in adult rats, indicating that the pharmacological manipulations caused only transient age-dependent changes. The study was thus in certain aspects successful in creating a novel approach to model social deficit potentially relevant to schizophrenia; other findings require further investigation.http://www.sciencedirect.com/science/article/pii/S2667242125000788SchizophreniaSocial behaviornegative symptomAnimal modelTwo-hit modelOxytocin |
| spellingShingle | Kristina Hakenova Anna Mikulecka Kristina Holubova Marketa Chvojkova Romana Slamberova Jana Jurcovicova Barbora Cechova Silvester Ponist Jiri Horacek Karel Vales A new two-hit animal model for schizophrenia research: Consequences on social behavior IBRO Neuroscience Reports Schizophrenia Social behavior negative symptom Animal model Two-hit model Oxytocin |
| title | A new two-hit animal model for schizophrenia research: Consequences on social behavior |
| title_full | A new two-hit animal model for schizophrenia research: Consequences on social behavior |
| title_fullStr | A new two-hit animal model for schizophrenia research: Consequences on social behavior |
| title_full_unstemmed | A new two-hit animal model for schizophrenia research: Consequences on social behavior |
| title_short | A new two-hit animal model for schizophrenia research: Consequences on social behavior |
| title_sort | new two hit animal model for schizophrenia research consequences on social behavior |
| topic | Schizophrenia Social behavior negative symptom Animal model Two-hit model Oxytocin |
| url | http://www.sciencedirect.com/science/article/pii/S2667242125000788 |
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