Ferrer-Pérez Carmen, Reguilón Marina D, Manzanedo Carmen, Miñarro José, Rodríguez-Arias Marta
Department of Psychobiology, Faculty of Psychology, Universitat de València, Valencia, Spain.
Front Behav Neurosci. 2019 Jul 4;13:148. doi: 10.3389/fnbeh.2019.00148. eCollection 2019.
Social defeat is considered the most representative animal model for studying the consequences of social stress. Intermittent social defeat (ISD) has proved to enhance the response to cocaine hedonic properties. In the present research, we evaluated if different social housing conditions, as housing with a familiar conspecific or with a female, exert a protective effect modulating the negative consequences of ISD as the increased sensitivity to cocaine and the induction of anxiety-like behavior. To achieve this objective, non-stressed or ISD OF1 male mice were divided into five different experimental groups according to their social environment: standard housing (four adult males per cage); male adolescent or adult in pairs (two males per cage); and adult males housed with a female for a short or long period (3 days vs. the whole duration of the study). Anxiety-like behavior was evaluated 19 days after the last episode of ISD using an elevated plus maze (EPM), and 24 h later the animals underwent a conditioned place preference paradigm (CPP) induced by a sub-threshold dose of cocaine (1 mg/kg). Following CPP, biological samples were taken to measure striatal levels of interleukin 6 (IL-6) and plasmatic levels of oxytocin (OT). Our results confirmed that ISD animals housed in standard condition displayed an anxious phenotype, developed CPP and had increased levels of IL-6 in the striatum. However, animals housed with a female or with a familiar male since adolescence did not develop CPP and were protected against the anxiogenic and neuroinflammatory potential of ISD stress. In the group of animals paired with a female throughout the experimental procedure, an increase in OT levels may have underlain this buffering effect, while the protective effect of being housed with a familiar male mouse seems to be related with a better resolution of the stress response. The present results expand our knowledge of the neurobiology of vulnerability to drug addiction and highlight the benefit of social support for recovery from the adverse effects of social stress.
社会挫败被认为是研究社会应激后果的最具代表性的动物模型。间歇性社会挫败（ISD）已被证明会增强对可卡因享乐特性的反应。在本研究中，我们评估了不同的群居条件，如与熟悉的同种动物或雌性动物一起饲养，是否能发挥保护作用，调节ISD的负面后果，如对可卡因敏感性增加和诱发焦虑样行为。为实现这一目标，将未受应激或经历ISD的OF1雄性小鼠根据其社会环境分为五个不同的实验组：标准饲养（每笼四只成年雄性）；成对饲养的雄性青少年或成年小鼠（每笼两只雄性）；以及与雌性动物短期或长期（3天与研究全程）一起饲养的成年雄性小鼠。在最后一次ISD发作19天后，使用高架十字迷宫（EPM）评估焦虑样行为，24小时后，动物接受由阈下剂量可卡因（1mg/kg）诱导的条件性位置偏爱范式（CPP）。CPP实验后，采集生物样本以测量纹状体白细胞介素6（IL-6）水平和血浆催产素（OT）水平。我们的结果证实，处于标准条件下的ISD动物表现出焦虑表型，形成了CPP，且纹状体中IL-6水平升高。然而，自青春期起就与雌性动物或熟悉的雄性动物一起饲养的动物未形成CPP，并免受ISD应激的致焦虑和神经炎症影响。在整个实验过程中与雌性动物配对的动物组中，OT水平的升高可能是这种缓冲作用的基础，而与熟悉的雄性小鼠一起饲养的保护作用似乎与应激反应的更好解决有关。目前的结果扩展了我们对药物成瘾易感性神经生物学的认识，并突出了社会支持对从社会应激不良影响中恢复的益处。
