Moles A, Sarli C, Bartolomucci A, D'Amato F R
Institute of Neuroscience, CNR, Via del Fosso di Fiorano 64, 00137 Roma, Italy.
Psychoneuroendocrinology. 2008 May;33(4):462-70. doi: 10.1016/j.psyneuen.2008.01.003. Epub 2008 Mar 4.
Early adverse experiences are preeminent factors for the development of affective disorders. In the present study, we analyzed the effects of different postnatal manipulations applied either on the mother or on the offspring in mice. Maternal behavior and adrenocortical activity of both mothers and offspring at the end of postnatal stress and at adulthood were considered.
From postnatal day (PND) 1 to 14 mice underwent 15min of: (a) brief (15min) pups' exposure to clean bedding (CB: clean bedding), (b) mothers' exposure to the odor of a novel male (SM: stressed mother) or (c) mothers' exposure to a clean cage (CSM: control stressed mother), and (d) standard rearing (N-H: non-handled). The behavior of mouse dams during and after stress sessions was analyzed. Serum corticosterone of mothers and pups at the end of the stress session and 30min after reunion was assessed on PND 14. Moreover, anxiety levels and HPA-axis inhibitory feedback in response to dexamethasone administration were evaluated in adult male offspring.
Overall, during the 14 days of treatment CB mothers when reunited with their pups showed higher maternal behavior than other dams. After the last stress (PND 14) SM and CSM maternal corticosterone levels increased as well as those of CB pups. While 30min of mother-infant interaction restored baseline corticosterone levels in SM and CSM mothers and in CB pups, SM and CSM offspring showed a decrease of corticosterone under baseline levels. At adulthood, SM and CSM males did not show the suppressive hormonal response to dexamethasone treatment. Moreover, adult CB and SM male mice displayed decreased anxiety in the open field.
Maternal psychosocial stress during lactation seems to permanently affect the offspring's HPA functioning. These effects may be dissociated from the behavioral response as suggested by the decrease of anxiety in SM and CB adult mice.
早期不良经历是情感障碍发生的首要因素。在本研究中,我们分析了对小鼠母亲或后代进行不同产后处理的影响。研究考虑了产后应激结束时和成年期母亲和后代的母性行为及肾上腺皮质活动。
从出生后第1天(PND)到第14天,小鼠接受15分钟的以下处理:(a)幼崽短暂(15分钟)暴露于干净垫料(CB:干净垫料),(b)母亲暴露于陌生雄性的气味(SM:应激母亲)或(c)母亲暴露于干净笼子(CSM:对照应激母亲),以及(d)标准饲养(N-H:未处理)。分析了应激期间及应激后母鼠的行为。在PND 14评估应激结束时及 reunion 后30分钟母亲和幼崽的血清皮质酮水平。此外,评估了成年雄性后代对给予地塞米松的焦虑水平和HPA轴抑制反馈。
总体而言,在14天的治疗期间,CB组母亲与幼崽 reunion 时表现出比其他母鼠更高的母性行为。在最后一次应激(PND 14)后,SM和CSM组母亲的皮质酮水平以及CB组幼崽的皮质酮水平均升高。虽然30分钟的母婴互动使SM和CSM组母亲以及CB组幼崽的皮质酮水平恢复到基线,但SM和CSM组后代的皮质酮水平降至基线以下。成年期,SM和CSM组雄性对地塞米松治疗未表现出激素抑制反应。此外,成年CB和SM组雄性小鼠在旷场试验中的焦虑水平降低。
哺乳期母亲的心理社会应激似乎会永久性地影响后代的HPA功能。这些影响可能与行为反应无关,如SM和CB成年小鼠焦虑水平降低所示。