Zurita A, Martijena I, Cuadra G, Brandão M L, Molina V
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000, Córdoba, Argentina.
Behav Brain Res. 2000 Dec 20;117(1-2):163-71. doi: 10.1016/s0166-4328(00)00302-8.
The present research studied the influence of an early chronic variable stress (CVS) paradigm - an animal model of depression - on behavioral responses to subsequent environmental challenges suggested to model anhedonia and emotional reactions such as anxiety and fear. In order to explore a potential involvement of an endogenous opiate mechanism - presumably activated during CVS exposure - in the development of such behavioral reactions, in all experiments rats were administered naltrexone (NAL, 2 mg/kg, i.p.) or vehicle (VH) prior to each daily stressor of the CVS procedure. Animals were exposed to CVS and 1 week later tested for sucrose preference (1%) in a free choice paradigm after the presentation or not of a 90-min restraint period. Only CVS treated animals that were later exposed to restraint showed a reduction of sucrose preference, this reduction was absent when CVS rats were pretreated previously with NAL. Moreover, CVS rats were one week later tested on the elevated plus maze (EPM) and in their conditioned and unconditioned freezing response to a single shock session. Early chronic stress resulted in an anxiogenic behavior in the EPM and in an enhanced conditioned and unconditioned freezing which were all abolished by NAL pretreatment. These behavioral findings suggest that the potential activation of an endogenous opiate mechanism during CVS participates in the development of anhedonia and exaggerated emotional reactions in response to subsequent stressful experiences.
本研究考察了一种早期慢性可变应激（CVS）范式——一种抑郁症动物模型——对后续环境挑战的行为反应的影响，这些环境挑战被认为可模拟快感缺失以及焦虑和恐惧等情绪反应。为了探究内源性阿片机制（可能在暴露于CVS期间被激活）在这些行为反应发展过程中的潜在作用，在所有实验中，在CVS程序的每日应激源之前，给大鼠腹腔注射纳曲酮（NAL，2毫克/千克）或赋形剂（VH）。动物暴露于CVS，1周后，在呈现或不呈现90分钟的束缚期后，在自由选择范式中测试蔗糖偏好（1%）。只有后来暴露于束缚的CVS处理动物表现出蔗糖偏好降低，当CVS大鼠预先用NAL预处理时，这种降低不存在。此外，1周后对CVS大鼠进行高架十字迷宫（EPM）测试，并测试它们对单次电击的条件性和非条件性僵住反应。早期慢性应激导致EPM中的焦虑行为以及增强的条件性和非条件性僵住，而这些都被NAL预处理消除。这些行为学结果表明，CVS期间内源性阿片机制的潜在激活参与了快感缺失的发展以及对后续应激经历的过度情绪反应。
