产前轻微应激易化由围产期注射引起的行为改变并弱化奥氮平的作用

产前母体处于应激状态下，可以削弱子代的神经系统对外界不良刺激影响的抵抗能力．但产前应激状态是否可以影响抗精神疾病药物对动物行为的增益作用，目前还没有明确的结论．此外，在动物实验中，动物需要经常接受注射操作，注射操作本身是否会影响动物行为，尚未有相关研究．在本实验中，探索了产前轻微应激状态、围产期注射操作和抗精神疾病药物对动物行为可能的交互影响．母鼠在经历产前轻微应激状态后生产子代，雄性仔鼠在围产期(日龄第7, 9, 11天)不接受注射或接受盐水或奥氮平注射(2 mg/kg，腹腔注射)．在其亚成年期(日龄第35天)和成年期(日龄第60天)，观察其社交和嗅觉辨识行为，分析了总探索时间和对新旧刺激的偏好程度两个参数．我们发现，围产期重复注射操作可以改变产前应激组大鼠在社交和嗅觉辨识实验中的偏好程度，对无应激组大鼠没有影响．奥氮平注射可以增长无应激组大鼠在社交活动中的总探索时间，对应激组大鼠没有影响．研究表明，产前轻微应激状态可以易化诸如围产期注射操作等不良环境刺激导致的行为异常，并减弱抗精神疾病药物的对神经系统的影响．

Mild Prenatal Stress Exposure Contributed to Behavioral Changes Induced by Postnatal Injections and Blocked The Effects of Olanzapine

Exposure of pregnant females to strong prenatal stress generally induces psychotic-like behavioral impairments in their offspring. In contrast to strong stress exposure, mild prenatal stress exposure (MPSE) has been reported to increase the vulnerability of the nervous system to adverse environmental stimuli. However, the impacts of MPSE on treatment with antipsychotic medication have not been well investigated. In addition, although commonly utilized in animal experiments, the potential influences of injections per se on animal behavior have not been evaluated. Here, we investigated how MPSE, postnatal injections and olanzapine (OLZ) treatment might interact to affect the behavior of rats. Pregnant female rats were exposed to mild stress or left undisturbed during the last week of gestation. Their offspring were divided into three sub-groups and subjected to injections with saline or OLZ (2 mg/kg) on postnatal days (PDs) 7, 9 and 11 or were left undisturbed without injection. Social and olfactory discrimination tests were performed during adolescent (PD 35) and adult (PD 60) periods. Total exploratory time and the degree of preference in the discrimination tests were measured. We found that postnatal injections changed the degree of preference in adolescent prenatally stressed rats but had no effect on the degree of preference in the non-stressed rats. OLZ treatment increased the social exploratory time in the non-stressed rats during the adolescent and adult periods. However, these enhancing effects were diminished in the prenatally stressed rats. Our results indicate that MPSE could contribute to the behavioral changes induced by adverse stimuli such as postnatal injections and could reduce the treatment effects of antipsychotic medication.