Sampedro-Viana Daniel, Cañete Toni, Ancil-Gascón Paula, Cisci Sonia, Tobeña Adolf, Fernández-Teruel Alberto
Medical Psychology Unit, Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.
Department of Life and Environmental Sciences and Center of Excellence for Neurobiology of Dependence, University of Cagliari, 09042 Cagliari, Italy.
Brain Sci. 2024 Sep 13;14(9):920. doi: 10.3390/brainsci14090920.
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.
啮齿动物的社交退缩是社交障碍的一种表现，是精神分裂症的一种重要阴性症状。据报道，罗马高回避（RHA）和低回避（RLA）大鼠品系在与精神分裂症相关的行为表型上表现出不同的特征。本研究聚焦于急性给予地佐环平（MK801，一种NMDA受体拮抗剂）后，这两种大鼠品系的社交和非社交行为，MK801是一种用于产生社交障碍和多动的精神分裂症样特征的药理学模型。此外，由于催产素（OXT）已被提议作为一种天然抗精神病药物以及治疗精神分裂症社交缺陷的潜在辅助疗法，我们评估了OXT给药的效果及其逆转MK801对社交和非社交行为的损害作用以及MK801诱导的多动的能力。给予MK801后，两种大鼠品系均出现活动过度以及社交和非社交行为减少，但这些药物效应在RHA大鼠中明显更显著。OXT（0.04 mg/kg和0.2 mg/kg）减弱了MK801在两种大鼠品系中诱导的活动过度，尽管这种效应在RHA大鼠中更显著。MK801对“社交洞”探索的减少作用仅在RLA大鼠中得到中度但显著的减弱。本研究首次证明了OXT对MK801在两种罗马大鼠品系中诱导的损害具有不同作用，为OXT对抗精神分裂症样症状（包括阳性样症状，即MK801诱导的活动过度；以及阴性样症状，即MK801导致的社交行为减少）的潜在治疗效果提供了一些支持，同时强调了遗传背景（即大鼠品系）在影响MK801和催产素作用方面的重要性。
