Hefner Kathryn, Cameron Heather A, Karlsson Rose-Marie, Holmes Andrew
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD 20852-9411, USA.
Behav Brain Res. 2007 Sep 4;182(2):344-8. doi: 10.1016/j.bbr.2007.03.032. Epub 2007 Apr 1.
Rodent models provide a valuable approach to elucidating the pathophysiological mechanisms underlying the deleterious effects of childhood trauma and stress. Neonatal rats and mice emit ultrasonic vocalizations (USVs) when separated from the dam and litter. USVs are suppressed in rat pups by exposure to the putatively infanticidal threat of an adult male. In the present study, C57BL/6J mouse pups were exposed to an anaesthetized (non-sire) adult C57BL/6J male for 3-min/day from postnatal days 2-14, and subsequently tested for anxiety-related behaviors (using the novel open field, elevated plus-maze, light/dark exploration tests) and depression-related behavior (using the forced swim test) at 11 weeks of age. In a separate cohort, hypothalamic-pituitary-adrenal-axis activation was measured via plasma corticosterone levels following either a single male-exposure or separation episode. Results showed that pups exposed to an adult male emitted significantly fewer USVs than separation-only counterparts. Corticosterone levels were significantly lower following single exposure to the adult male than separation alone. Repeated neonatal male-exposure did not lead to significant alterations in anxiety- or depression-related behaviors in adulthood. Taken together, present data suggest that the form of adult male-exposure employed did not act as a significant stressor, at least in this mouse strain. Further studies will be needed to determine whether alternative mouse strains, exposure protocols or adult behavioral assays will produce a different pattern of short-term and long-term effects.
啮齿动物模型为阐明童年创伤和应激有害影响背后的病理生理机制提供了一种有价值的方法。新生大鼠和小鼠在与母鼠和同窝幼崽分离时会发出超声波叫声（USV）。暴露于成年雄性可能的杀婴威胁下，大鼠幼崽的USV会受到抑制。在本研究中，从出生后第2天至14天，每天将C57BL/6J小鼠幼崽暴露于麻醉的（非父系）成年C57BL/6J雄性大鼠3分钟，随后在11周龄时测试其焦虑相关行为（使用新颖的旷场试验、高架十字迷宫试验、明暗探索试验）和抑郁相关行为（使用强迫游泳试验）。在另一个队列中，通过单次雄性暴露或分离事件后血浆皮质酮水平测量下丘脑-垂体-肾上腺轴的激活情况。结果显示，暴露于成年雄性的幼崽发出的USV明显少于仅经历分离的幼崽。单次暴露于成年雄性后，皮质酮水平显著低于仅分离的情况。重复的新生期雄性暴露在成年期并未导致焦虑或抑郁相关行为的显著改变。综上所述，目前的数据表明，至少在这种小鼠品系中，所采用的成年雄性暴露形式并非显著的应激源。需要进一步的研究来确定替代的小鼠品系、暴露方案或成年行为测定是否会产生不同的短期和长期影响模式。
