Barros Virginia G, Rodríguez Pablo, Martijena Irene D, Pérez Adriana, Molina Victor A, Antonelli Marta C
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Synapse. 2006 Dec 15;60(8):609-18. doi: 10.1002/syn.20336.
Chronic maternal stress during pregnancy has been associated with behavioral alterations that persist into adulthood. Moreover, adoption procedures performed immediately after birth can reverse these alterations. In this study, we examined the effects of prenatal restraint stress and adoption at birth (cross-fostering) on the behavioral response to an anxiety-provoking situation and on the adult male offspring expression of benzodiazepine (BDZ) receptors in selected brain areas. Adult offspring of rats stressed during the last week of pregnancy exhibited higher levels of anxiety than control rats. The anxiogenic behavior found at the elevated plus maze (EPM) has been related to the reduced levels of BDZ receptor levels in specific brain areas. Adult offspring of rats stressed during pregnancy exhibited a decrease in the number of BDZ receptors binding sites in the central amygdaloid nucleus (Ce), CA1, CA3, and the dentate gyrus regions of the hippocampus when compared to controls. Regarding the adoption procedure, control pups raised by a foster gestationally stressed mother showed similar levels of anxiety as stressed groups. Stressed offspring raised by a foster control mother showed reduced anxiety levels compared to that of the control groups. Adoption per se showed no difference in time spent, neither in the open arms of the plus maze nor in BDZ receptor levels, when compared to the corresponding control and stressed groups. Stressed offspring raised by a foster control mother reverted BDZ receptor levels to control values. However, control pups raised by a gestationally stressed foster mother showed similar values compared to the control offspring in hippocampus, in spite of showing an anxiogenic behavior in the EPM. We found a significant increase of Ce BDZ receptor levels in control offspring raised by a foster stressed mother that could be explained as a compensatory effect to a GABA receptor desensitization. In summary, the behavioral outcome of the adult offspring is vulnerable both to the stress experience during the late prenatal period as well as to possible variations in care during lactation by mothers subjected to chronic stress during gestation. There seems to be a direct correlation between anxiety state and BDZ receptor levels in the adult offspring raised by their biological mothers. However, the mechanism of BDZ regulation leading to an anxious behavior might be different if the insult is received only postnatally as opposed to both pre and postnatally.
孕期母亲长期处于应激状态与持续至成年期的行为改变有关。此外，出生后立即进行的领养程序可逆转这些改变。在本研究中，我们考察了产前束缚应激及出生时领养（交叉寄养）对焦虑诱发情境下行为反应以及成年雄性后代特定脑区苯二氮䓬（BDZ）受体表达的影响。孕期最后一周受到应激的大鼠成年后代比对照大鼠表现出更高水平的焦虑。高架十字迷宫（EPM）中发现的致焦虑行为与特定脑区BDZ受体水平降低有关。与对照相比，孕期受到应激的大鼠成年后代在杏仁中央核（Ce）、海马CA1、CA3及齿状回区域的BDZ受体结合位点数量减少。关于领养程序，由孕期受到应激的养母抚养的对照幼崽表现出与应激组相似的焦虑水平。由对照养母抚养的应激后代与对照组相比焦虑水平降低。与相应的对照和应激组相比，领养本身在十字迷宫开放臂停留时间或BDZ受体水平方面无差异。由对照养母抚养的应激后代BDZ受体水平恢复至对照值。然而，尽管在EPM中表现出致焦虑行为，但由孕期受到应激的养母抚养的对照幼崽在海马中的表现与对照后代相似。我们发现由应激养母抚养的对照后代Ce区BDZ受体水平显著升高，这可解释为对GABA受体脱敏的一种代偿效应。总之，成年后代的行为结果既易受产前后期应激经历的影响，也易受孕期遭受慢性应激的母亲在哺乳期护理可能变化的影响。由亲生母亲抚养的成年后代的焦虑状态与BDZ受体水平之间似乎存在直接关联。然而，如果仅在出生后而非出生前后都受到损害，导致焦虑行为的BDZ调节机制可能不同。
