Reduced activity of the noradrenergic system in the paraventricular nucleus at the end of pregnancy: Implications for stress hyporesponsiveness
Reduced activity of the noradrenergic system in the paraventricular nucleus at the end of pregnancy: Implications for stress hyporesponsiveness
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DOI：
10.1111/j.1365-2826.2005.01272.x
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Neumann, ID
中科院分区：
文献类型：
--
作者：
Douglas, AJ;Meddle, SL;Neumann, ID
我们研究了下丘脑中去甲肾上腺素神经传递的变化是否可以解释妊娠晚期下丘脑-垂体-肾上腺（HPA）轴的低反应性。去甲肾上腺素释放下丘脑室旁核在游泳应激反应，估计微透析和高效液相色谱法，是较低的孕20天的大鼠相比，处女大鼠。驱动中枢去甲肾上腺素能通路使用静脉注射胆囊收缩素增加促肾上腺皮质激素（ACTH）的分泌在处女大鼠，但反应显着减少在16天和20天的孕鼠。因此，去甲肾上腺素能输入到室旁核和HPA轴的活动在妊娠晚期减弱。在暴露于游泳应激之前和期间，通过脑室内注射α（1）受体拮抗剂苯诺沙坦，研究了妊娠期HPA轴对去甲肾上腺素的敏感性。在处女大鼠中，苯诺沙坦增加基础和应激诱导的ACTH分泌，但在晚期妊娠大鼠中，苯诺沙坦的作用减弱，表明HPA轴对去甲肾上腺素神经传递的敏感性降低和/或系统此时无法解除抑制。通过原位杂交测定，与未孕大鼠相比，妊娠晚期大鼠室旁核小细胞和大细胞中α（1A）-肾上腺素受体mRNA表达降低。此外，阻断内源性阿片抑制纳洛酮预处理恢复ACTH分泌反应胆囊收缩素在怀孕的大鼠。因此，在妊娠晚期，室旁核的去甲肾上腺素能输入减少，室旁核的α（1A）受体表达减少，这两者都可能导致妊娠期HPA轴反应性降低。
We investigated whether changes in noradrenaline neurotransmission in the hypothalamus could explain the hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in late pregnancy. Noradrenaline release within the hypothalamic paraventricular nucleus in response to swim stress, as estimated by microdialysis and high-performance liquid chromatography, was lower in 20-day pregnant rats compared to virgin rats. Driving a central noradrenergic pathway using intravenous cholecystokinin increased adrenocorticotropic hormone (ACTH) secretion in virgin rats, but the response was significantly less in 16-day and 20-day pregnant rats. Thus, the activity of noradrenergic inputs to the paraventricular nucleus and the HPA axis is attenuated in late pregnancy. The sensitivity of the HPA axis to noradrenaline in pregnancy was investigated by intracerebroventricular administration of an alpha(1)-receptor antagonist, benoxathian, before and during exposure to swim stress. In virgin rats, benoxathian increased basal and stress-induced ACTH secretion, but in late pregnant rats the benoxathian effects were attenuated, indicating reduced sensitivity of the HPA axis to noradrenaline neurotransmission and/or the inability of the system to become disinhibited at this time. alpha(1A)-adrenoreceptor mRNA expression in the parvocellular and magnocellular paraventricular nucleus, measured by in situ hybridisation, was decreased in late pregnant compared to virgin rats. Additionally, blocking endogenous opioid inhibition with naloxone pretreatment restored the ACTH secretory response to cholecystokinin in pregnant rats. Thus, in late pregnancy, there is reduced noradrenergic input to the paraventricular nucleus and reduced alpha(1A)-receptor expression in the paraventricular nucleus, both of which may contribute to the reduced responsiveness of the HPA axis in pregnancy.