a3f27f81554eb992c9c26df11f115180 pmc_11430565.pdf 8c73b6542c24d817bded99573d3ec817d74f7913 pmc_11430565.pdf eb717906004fde16c79ab91c7a0f4f7a21b2d5d1ea0620d8b02bbc9bb4a74a8e pmc_11430565.pdf Title: Contrasting Effects of Oxytocin on MK801-Induced Social and Non-Social Behavior Impairment and Hyperactivity in a Genetic Rat Model of Schizophrenia-Linked Features Subject: Social withdrawal in rodents is a measure of asociality, an important negative symptom of schizophrenia. The Roman high- (RHA) and low-avoidance (RLA) rat strains have been reported to exhibit differential profiles in schizophrenia-relevant behavioral phenotypes. This investigation was focused on the study of social and non-social behavior of these two rat strains following acute administration of dizocilpine (MK801, an NMDA receptor antagonist), a pharmacological model of schizophrenia-like features used to produce asociality and hyperactivity. Also, since oxytocin (OXT) has been proposed as a natural antipsychotic and a potential adjunctive therapy for social deficits in schizophrenia, we have evaluated the effects of OXT administration and its ability to reverse the MK801-impairing effects on social and non-social behavior and MK801-induced hyperactivity. MK801 administration produced hyperlocomotion and a decrease in social and non-social behavior in both rat strains, but these drug effects were clearly more marked in RHA rats. OXT (0.04 mg/kg and 0.2 mg/kg) attenuated MK801-induced hyperlocomotion in both rat strains, although this effect was more marked in RHA rats. The MK801-decreasing effect on exploration of the “social hole” was moderately but significantly attenuated only in RLA rats. This study is the first to demonstrate the differential effects of OXT on MK801-induced impairments in the two Roman rat strains, providing some support for the potential therapeutic effects of OXT against schizophrenia-like symptoms, including both a positive-like symptom (i.e., MK801-induced hyperlocomotion) and a negative-like symptom (i.e., MK801 decrease in social behavior), while highlighting the importance of the genetic background (i.e., the rat strain) in influencing the effects of both MK801 and oxytocin. Keywords: RHA and RLA rats; schizophrenia; social interaction; hyperactivity; oxytocin; NMDA receptor antagonist; MK801 Author: Daniel Sampedro-Viana, Toni Cañete, Paula Ancil-Gascón, Sonia Cisci, Adolf Tobeña and Alberto Fernández-Teruel Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Sat Sep 14 10:40:31 2024 CEST ModDate: Sat Sep 14 10:46:18 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1135685 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ENXZUH+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 TTSBRD+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 EKQEMN+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 SQLKFR+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 LOJQEZ+VnURWPalladioL Type 1 Custom yes yes yes 32 0 SLUQMQ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 IBIKHZ+CMSY10 Type 1 Builtin yes yes yes 65 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 78 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 82 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 86 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 90 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 97 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 104 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 123 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 127 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 131 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 135 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 142 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 149 0 Arial,Italic TrueType WinAnsi no no no 159 0 Arial TrueType WinAnsi no no no 162 0 Arial,Bold TrueType WinAnsi no no no 165 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 177 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 181 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 185 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 189 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 196 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 203 0 Arial,Italic TrueType WinAnsi no no no 213 0 Arial TrueType WinAnsi no no no 216 0 Arial,Bold TrueType WinAnsi no no no 219 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-06 02:47:56 CET RepresentationInformation: pmc_11430565.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-10-09 02:36:28 CEST Size: 1135685 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 452 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Subjects Destination: subsection.2.1 Item: Title: Social Interaction Destination: subsection.2.2 Item: Title: Drug Treatment and Experimental Groups Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Contrasting Effects of Oxytocin on MK801-Induced Social and Non-Social Behavior Impairment and Hyperactivity in a Genetic Rat Model of Schizophrenia-Linked Features Author: Daniel Sampedro-Viana, Toni Cañete, Paula Ancil-Gascón, Sonia Cisci, Adolf Tobeña and Alberto Fernández-Teruel Subject: Social withdrawal in rodents is a measure of asociality, an important negative symptom of schizophrenia. The Roman high- (RHA) and low-avoidance (RLA) rat strains have been reported to exhibit differential profiles in schizophrenia-relevant behavioral phenotypes. This investigation was focused on the study of social and non-social behavior of these two rat strains following acute administration of dizocilpine (MK801, an NMDA receptor antagonist), a pharmacological model of schizophrenia-like features used to produce asociality and hyperactivity. Also, since oxytocin (OXT) has been proposed as a natural antipsychotic and a potential adjunctive therapy for social deficits in schizophrenia, we have evaluated the effects of OXT administration and its ability to reverse the MK801-impairing effects on social and non-social behavior and MK801-induced hyperactivity. MK801 administration produced hyperlocomotion and a decrease in social and non-social behavior in both rat strains, but these drug effects were clearly more marked in RHA rats. OXT (0.04 mg/kg and 0.2 mg/kg) attenuated MK801-induced hyperlocomotion in both rat strains, although this effect was more marked in RHA rats. The MK801-decreasing effect on exploration of the “social hole” was moderately but significantly attenuated only in RLA rats. This study is the first to demonstrate the differential effects of OXT on MK801-induced impairments in the two Roman rat strains, providing some support for the potential therapeutic effects of OXT against schizophrenia-like symptoms, including both a positive-like symptom (i.e., MK801-induced hyperlocomotion) and a negative-like symptom (i.e., MK801 decrease in social behavior), while highlighting the importance of the genetic background (i.e., the rat strain) in influencing the effects of both MK801 and oxytocin. 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