A cholecystokinin-mediated pathway to the paraventricular thalamus is recruited in chronically stressed rats and regulates hypothalamic-pituitary-adrenal function
A cholecystokinin-mediated pathway to the paraventricular thalamus is recruited in chronically stressed rats and regulates hypothalamic-pituitary-adrenal function
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DOI：
10.1523/jneurosci.20-14-05564.2000
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发表时间：
2000-07-15
影响因子：
5.3
通讯作者：
Dallman, MF
中科院分区：
文献类型：
--
作者：
Bhatnagar, S;Viau, V;Dallman, MF
慢性应激改变下丘脑-垂体-肾上腺（HPA）对急性、新应激的反应。急性抑制后，慢性冷应激大鼠室旁丘脑核（pPVTh）后分裂表达fos的神经元数量比应激初始对照组增加。此外，PVTh损伤仅在先前应激的大鼠中增加HPA活性，这表明PVTh对HPA活性有抑制作用，但这种抑制作用仅发生在长期应激的大鼠中。在本研究中，我们进一步研究了慢性应激大鼠pPVTh的功能。我们通过注射逆行示踪剂氟金确定了pPVTh的传入投影。在含有氟金标记细胞的部位，含有氟金的臂旁外侧、导水管周围灰质和中缝背的神经元也表达胆囊收缩素（CCK） mRNA。然后，我们检查了这些CCKergic输入到pPVTh是否参与慢性应激后对急性新抑制的HPA反应。我们将CCK-B受体拮抗剂PD 135,158注射到对照组和慢性冷应激大鼠的PVTh中。PD 135,158仅在慢性应激大鼠中增强了ACTH对约束应激的反应，而在对照组中则没有。此外，CCK-B受体mRNA在pPVTh中的表达不受慢性冷胁迫的影响。我们得出结论，以前的慢性应激特别促进CCK释放到pPVTh，以应对急性，新的应激。CCK可能是由外侧臂旁、导水管周围灰质和/或中缝背核的神经元分泌的。CCK通过pPVTh中的CCK- b受体起作用，然后在长期应激而非初始大鼠中限制促进ACTH对新应激的反应。这些结果清楚地表明，慢性应激招募了一套新的途径来调节HPA对新应激的反应。
Chronic stress alters hypothalamic-pituitary-adrenal (HPA) responses to acute, novel stress. After acute restraint, the posterior division of the paraventricular thalamic nucleus (pPVTh) exhibits increased numbers of Fos-expressing neurons in chronically cold-stressed rats compared with stress-naive controls. Furthermore, lesions of the PVTh augment HPA activity in response to novel restraint only in previously stressed rats, suggesting that the PVTh is inhibitory to HPA activity but that inhibition occurs only in chronically stressed rats. In this study, we further examined pPVTh functions in chronically stressed rats. We identified afferent projections to the pPVTh using injection of the retrograde tracer fluorogold. Of the sites containing fluorogold-labeled cells, neurons in the lateral parabrachial, periaqueductal gray, and dorsal raphe containing fluorogold also expressed cholecystokinin (CCK) mRNA. We then examined whether these CCKergic inputs to the pPVTh were involved in HPA responses to acute, novel restraint after chronic stress. We injected the CCK-B receptor antagonist PD 135,158 into the PVTh before restraint in control and chronically cold-stressed rats. ACTH responses to restraint stress were augmented by PD 135,158 only in chronically stressed rats but not in controls. In addition, CCK-B receptor mRNA expression in the pPVTh was not altered by chronic cold stress. We conclude that previous chronic stress specifically facilitates the release of CCK into the pPVTh in response to acute, novel stress. The CCK is probably secreted from neurons in the lateral parabrachial, the periaqueductal gray, and/or the dorsal raphe nuclei. Acting via CCK-B receptors in pPVTh, CCK then constrains facilitated ACTH responses to novel stress in chronically stressed but not naive rats. These results demonstrate clearly that chronic stress recruits a new set of pathways that modulate HPA responsiveness to a novel stress.