Calpe-López Claudia, García-Pardo Maria Pilar, Martínez-Caballero Maria Angeles, Santos-Ortíz Alejandra, Aguilar Maria Asunción
Neurobehavioural Mechanisms and Endophenotypes of Addictive Behavior Research Unit, Department of Psychobiology, University of Valencia, Valencia, Spain.
Department of Psychology and Sociology, Faculty of Social Sciences, University of Zaragoza, Teruel, Spain.
Front Behav Neurosci. 2020 Jan 9;13:278. doi: 10.3389/fnbeh.2019.00278. eCollection 2019.
The relationship between stress and drug use is well demonstrated. Stress-induced by repeated social defeat (RSD) enhances the conditioned place preference (CPP) induced by cocaine in mice. The phenomenon of resilience understood as the ability of subjects to overcome the negative effects of stress is the focus of increasing interest. Our aim is to characterize the behavior of resilient animals with respect to the effects of RSD on the CPP induced by cocaine. To this end, 25 male C57BL/6 mice were exposed to stress by RSD during late adolescence, while other 15 male mice did not undergo stress (controls). On the 2 days following the last defeat, all the animals carried out the elevated plus maze (EPM) and Hole Board, Social Interaction, Tail Suspension and Splash tests. Three weeks later, all the animals performed the CPP paradigm with a low dose of cocaine (1 mg/kg). Exposure to RSD decreased all measurements related to the open arms of the EPM. It also reduced social interaction, immobility in the tail suspension test (TST) and grooming in the splash test. RSD exposure also increased the sensitivity of the mice to the rewarding effects of cocaine, since only defeated animals acquired CPP. Several behavioral traits were related to resilience to the potentiating effect of RSD on cocaine CPP. Mice that showed less submission during defeat episodes, a lower percentage of time in the open arms of the EPM, low novelty-seeking, high social interaction, greater immobility in the TST and a higher frequency of grooming were those that were resilient to the long-term effects of social defeat on cocaine reward since they behaved like controls and did not develop CPP. These results suggest that the behavioral profile of resilient defeated mice is characterized by an active coping response during episodes of defeat, a greater concern for potential dangers, less reactivity in a situation of inevitable moderate stress and fewer depressive-like symptoms after stress. Determining the neurobehavioral substrates of resilience is the first step towards developing behavioral or pharmacological interventions that increase resilience in individuals at a high risk of suffering from stress.
应激与药物使用之间的关系已得到充分证明。重复社会挫败（RSD）诱导的应激增强了可卡因在小鼠中诱导的条件性位置偏爱（CPP）。复原力现象被理解为个体克服应激负面影响的能力，正日益受到关注。我们的目的是描述具有复原力的动物在RSD对可卡因诱导的CPP影响方面的行为特征。为此，25只雄性C57BL/6小鼠在青春期后期暴露于RSD诱导的应激中，而另外15只雄性小鼠未经历应激（对照组）。在最后一次挫败后的两天，所有动物进行高架十字迷宫（EPM）、洞板、社交互动、悬尾和喷水试验。三周后，所有动物用低剂量可卡因（1mg/kg）进行CPP范式试验。暴露于RSD降低了所有与EPM开放臂相关的测量值。它还减少了社交互动、悬尾试验（TST）中的不动时间以及喷水试验中的梳理行为。RSD暴露还增加了小鼠对可卡因奖赏作用的敏感性，因为只有受挫败的动物获得了CPP。一些行为特征与对RSD增强可卡因CPP作用的复原力有关。在挫败事件中表现出较少顺从、在EPM开放臂中停留时间百分比较低、低新奇寻求、高社交互动、在TST中更大的不动性以及更高梳理频率的小鼠，对社会挫败对可卡因奖赏的长期影响具有复原力，因为它们的行为类似于对照组，且未出现CPP。这些结果表明，具有复原力的受挫败小鼠的行为特征是在挫败事件中表现出积极的应对反应、对潜在危险有更大的关注、在不可避免的中度应激情况下反应性较低以及应激后较少出现类抑郁症状。确定复原力的神经行为基础是开发行为或药理学干预措施以提高处于高应激风险个体复原力的第一步。
