Contrasting Effects of Oxytocin on MK801-Induced Social and Non-Social Behavior Impairment and Hyperactivity in a Genetic Rat Model of Schizophrenia-Linked Features
Sampedro-Viana, Daniel (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Cañete, Toni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Ancil-Gascón, Paula (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Cisci, Sonia (University of Cagliari)
Tobeña, Adolf 1950- (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Fernández-Teruel, Alberto (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)

Date:	2024
Abstract:	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.
Grants:	Agencia Estatal de Investigación PID2020-114697GB-I00 Agencia Estatal de Investigación PID2023-147693NB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00557
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	RHA and RLA rats ; Schizophrenia ; Social interaction ; Hyperactivity ; Oxytocin ; NMDA receptor antagonist ; MK801
Published in:	Brain sciences, Vol. 14 (september 2024) , ISSN 2076-3425

DOI: 10.3390/brainsci14090920
PMID: 39335415

12 p, 1.1 MB

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