Imipramine ameliorates early life stress-induced alterations in synaptic plasticity in the rat lateral amygdala
Imipramine ameliorates early life stress-induced alterations in synaptic plasticity in the rat lateral amygdala
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DOI：
10.1016/j.bbr.2016.09.065
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发表时间：
2017-01-15
影响因子：
2.7
通讯作者：
Hess, Grzegorz
中科院分区：
文献类型：
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作者：
Danielewicz, Joanna;Trenk, Aleksandra;Hess, Grzegorz
长期增强（LTP）和长期抑制（LTD）是皮层和丘脑输入侧杏仁核（LA）的两种相反形式的突触可塑性。研究表明，母鼠幼崽的分离（MS）会导致青春期LTP和LTD通路的潜力发生变化。丙咪嗪是一种原型三环抗抑郁药，已被证明可以抵消MS对大鼠行为的一些有害影响，但尚不清楚MS诱导的LA双向突触可塑性的改变是否可以通过丙咪嗪治疗逆转。为此，大鼠幼仔在出生后1-21天（PNDs）接受MS（3小时/天）。在每个pnd 29-42中，先前遭受MS的雄性大鼠皮下注射丙咪嗪（10 mg/kg）。在体外记录含有LA的切片的场电位，并诱导LTP和LTD达到饱和水平。在丘脑输入到LA时，与对照动物相比，MS大鼠的最大LTP和最大LTD都减少了，证实了之前的结果。然而，这些影响不再存在于大鼠遭受MS和后来用丙咪嗪治疗。在ms刺激大鼠的皮层输入处，观察到最大LTP的损伤和最大LTD的增强。在接受丙咪嗪治疗的MS大鼠皮层输入处，LTD水平与对照组相当，但丙咪嗪并没有恢复该输入下LTP的潜力。这些结果表明丙咪嗪完全逆转MS在丘脑-杏仁核通路的作用，然而，在皮质-杏仁核通路中，丙咪嗪部分逆转MS的作用。(C) 2016 Elsevier B.V.版权所有
Long-term potentiation (LTP) and long-term depression (LTD) are two opposite forms of synaptic plasticity at the cortical and thalamic inputs to the lateral amygdala (LA). It has been demonstrated that maternal separation (MS) of rat pups results in alterations in the potential for both pathways to undergo LTP and LTD in adolescence. Imipramine, a prototypic tricyclic antidepressant, has been shown to counteract some detrimental effects of MS on rat behavior, however it is not known whether MS-induced alterations in the potential for bidirectional synaptic plasticity in the LA could be reversed by imipramine treatment. To this end, rat pups were subjected to MS (3 h/day) on postnatal days (PNDs) 1-21. On each of PNDs 29-42, male rats previously subjected to MS were injected subcutaneously with imipramine (10 mg/kg). Field potentials were recorded ex vivo from slices containing the LA and saturating levels of LTP and LTD were induced. At the thalamic input to the LA, both the maximum LTP and the maximum LTD were reduced in rats subjected to MS when compared to control animals, confirming earlier results. However, these effects were no longer present in rats subjected to MS and later treated with imipramine. At the cortical input in slices prepared from MS-subjected rats, an impairment of the maximum LTP and an enhancement of the maximum LTD were observed. At the cortical input in rats subjected to MS and receiving imipramine treatment, the level of LTD was comparable to control but imipramine did not restore the potential for LTP at this input. These results demonstrate that imipramine fully reverses the effects of MS in the thalamo-amygdalar pathway, however, in the cortico-amygdalar pathway the reversal of the effects of MS by imipramine is partial. (C) 2016 Elsevier B.V. All rights reserved.