School of Biomedical Sciences and Pharmacy and the Centre for Brain and Mental Health Research, University of Newcastle, and The Hunter Medical Research Institute, Newcastle, Australia.
Neuroscience. 2010 Aug 25;169(2):733-42. doi: 10.1016/j.neuroscience.2010.05.005. Epub 2010 May 15.
At present, exposure of a rodent to the odour of a predator is one of the most common animal models of post traumatic stress disorder (PTSD). Despite this, the model remains incompletely characterized, particularly in regard to within subject assessment of major PTSD-like behaviours. In an attempt to redress this situation, we have extensively characterized the two broad categories of behaviour that are considered to characterize PTSD, that is sensitized behaviours such as social withdrawal and hypervigilance and conditioned behaviours such as avoidance of trauma linked cues. Specifically, we determined the presence and duration of both conditioned and sensitized behaviours, in the same cohort of animals, after three exposures to predator odour. Conditioned fear was assessed on the basis of inhibition of locomotor activity upon return to context 2, 7, 14, 21, and 28 days after the last odour exposure session. To assess the impact on sensitization behaviours, we monitored acoustic startle responses and social interaction behaviour 4, 9, 16, 23, and 30 days after the last exposure session. In addition to examining the behavioural consequences associated with odour exposure, we also determined the key brain regions that were activated using DeltaFosB immunohistochemistry. Our results show that the two groups of behaviours thought to characterize PTSD (conditioned and sensitized) do not travel together in the predator odour model, with clear evidence of enduring changes in conditioned fear but little evidence of changes in social interaction or acoustic startle. With regard to associated patterns of activity in the brain, we observed that odour-exposed animals exhibited significantly higher numbers of FosB-positive nuclei in only the medial prefrontal cortex (mPFC), a finding that can be viewed as being consistent with the observed behavioural changes.
目前,暴露于捕食者气味是创伤后应激障碍(PTSD)最常见的动物模型之一。尽管如此,该模型仍未得到充分描述,特别是在对主体 PTSD 样行为的评估方面。为了弥补这种情况,我们广泛描述了被认为是 PTSD 特征的两种广泛行为类别,即社交回避和过度警惕等敏化行为,以及避免与创伤相关线索等条件行为。具体来说,我们在同一批动物中,在经历三次捕食者气味暴露后,确定了条件和敏化行为的存在和持续时间。条件恐惧是基于动物在最后一次气味暴露后第 2、7、14、21 和 28 天返回环境时抑制运动活动来评估的。为了评估对敏化行为的影响,我们在最后一次暴露后第 4、9、16、23 和 30 天监测了声学惊跳反应和社交互动行为。除了检查与气味暴露相关的行为后果外,我们还使用 DeltaFosB 免疫组织化学确定了被激活的关键大脑区域。我们的结果表明,被认为是 PTSD 特征的两种行为(条件和敏化)在捕食者气味模型中不会一起发生,条件恐惧有明显的持久变化,但社交互动或声学惊跳变化的证据很少。关于相关的大脑活动模式,我们观察到,暴露于气味的动物仅在前扣带回皮层(mPFC)中表现出明显更高数量的 FosB 阳性核,这一发现可以被视为与观察到的行为变化一致。