Hebb Andrea L O, Zacharko Robert M, Gauthier Michelle, Drolet Guy
Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Brain Res. 2003 Aug 29;982(2):195-210. doi: 10.1016/s0006-8993(03)03008-7.
The present investigation assessed the propensity of an acute psychogenic stressor exposure to induce behavioral change in paradigms assessing fear/anxiety (acoustic startle) and motivation/anhedonia (intracranial self-stimulation) in CD-1 mice. In the acoustic startle paradigm, a 10-min exposure of 2-4 month old mice (young adult mice) to fox odor (2,5-dihydro-2,4,5-trimethylthiazoline; TMT) was associated with decreased acoustic startle relative to mice exposed to the control odor, butyric acid (BA), immediately and relative to both saline and BA exposure 24 h following odor exposure in the home cage. In contrast, a 2-min exposure of young adult mice to TMT was associated with an increase in startle relative to saline and BA during the immediate post-odor test session only. In young adult mice a 2-min and a 10-min exposure to BA resulted in a startle profile of mice reminiscent of saline-treated mice. In comparison to young adult mice, a 2-min exposure of mature adult mice (5-7 months old) to TMT enhanced startle for up to 48 h relative to both saline and BA, while a 10-min exposure of mature adult mice to TMT enhanced startle for 168 h post-odor exposure relative to saline-exposed mice only. However, the greatest increase in startle amplitude (i.e. 48 h) was acquired following the 2-min exposure of mature mice to TMT. Among mature adult mice, a 10-min exposure to BA in the home cage eventuated in enhanced startle relative to saline-exposed animals 168 h following odor exposure. In comparison, exposure of mice to 10 min of TMT depressed responding for VTA brain stimulation at the initial 80 Hz frequency, but was ineffective in elevating reward thresholds relative to mice merely exposed to saline. Mice assessed in the ICSS paradigm were approximately 2-4 months old at the time of surgery and 5-7 months old at the completion of testing. These data suggest that acute odor exposure may induce a fear gradient dependent upon the perceived stressor severity and that the resultant anxiety-like effects are dependent on the duration of odor exposure, age of the animals and the temporal interval between odor presentation and behavioral testing. Moreover, the anxiogenic properties of psychogenic stressors can be separated from their anhedonic effects. The implications of these data for clinical psychopathology are discussed.
本研究评估了急性心理应激源暴露在评估恐惧/焦虑（听觉惊吓）和动机/快感缺失（颅内自我刺激）的范式中诱导CD-1小鼠行为变化的倾向。在听觉惊吓范式中，将2至4月龄小鼠（年轻成年小鼠）暴露于狐狸气味（2,5-二氢-2,4,5-三甲基噻唑啉；TMT）10分钟，与暴露于对照气味丁酸（BA）的小鼠相比，立即以及在气味暴露24小时后于饲养笼中与生理盐水和BA暴露相比，听觉惊吓反应降低。相比之下，仅在气味暴露后的即时测试阶段，将年轻成年小鼠暴露于TMT 2分钟与相对于生理盐水和BA的惊吓反应增加有关。在年轻成年小鼠中，暴露于BA 2分钟和10分钟会导致小鼠的惊吓反应模式类似于生理盐水处理的小鼠。与年轻成年小鼠相比，将成熟成年小鼠（5至7月龄）暴露于TMT 2分钟相对于生理盐水和BA在长达48小时内增强了惊吓反应，而将成熟成年小鼠暴露于TMT 10分钟相对于仅暴露于生理盐水的小鼠在气味暴露后168小时内增强了惊吓反应。然而，成熟小鼠暴露于TMT 2分钟后获得了最大的惊吓幅度增加（即48小时）。在成熟成年小鼠中，在饲养笼中暴露于BA 10分钟在气味暴露168小时后相对于暴露于生理盐水的动物导致惊吓反应增强。相比之下，将小鼠暴露于TMT 10分钟在最初80Hz频率下抑制了对腹侧被盖区脑刺激的反应，但相对于仅暴露于生理盐水的小鼠，在提高奖励阈值方面无效。在ICSS范式中评估的小鼠在手术时约为2至4月龄，在测试完成时为5至7月龄。这些数据表明，急性气味暴露可能会根据感知到的应激源严重程度诱导恐惧梯度，并且由此产生的焦虑样效应取决于气味暴露的持续时间、动物年龄以及气味呈现与行为测试之间的时间间隔。此外，心理应激源的致焦虑特性可以与其快感缺失效应分开。讨论了这些数据对临床精神病理学的意义。
