PREVIOUS STRESS ALTERS CORTICOTROPIN-RELEASING FACTOR NEUROTRANSMISSION IN THE LOCUS-COERULEUS
PREVIOUS STRESS ALTERS CORTICOTROPIN-RELEASING FACTOR NEUROTRANSMISSION IN THE LOCUS-COERULEUS
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DOI：
10.1016/0306-4522(94)00496-r
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发表时间：
1995-03-01
期刊：
影响因子：
3.3
通讯作者：
VALENTINO, RJ
中科院分区：
文献类型：
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作者：
CURTIS, AL;PAVCOVICH, LA;VALENTINO, RJ
在有应激史的大鼠中表征了蓝斑神经元的自发放电和应激诱发放电。每天接受一次或五次每次 30 分钟的足部电击的大鼠用氟烷麻醉，并在最后一次治疗后立即进行手术准备蓝斑单单位记录。急性和反复应激大鼠和对照组之间的蓝斑自发放电率和坐骨神经刺激引起的放电具有可比性。相反，在急性应激大鼠中，脑室内给予促肾上腺皮质激素释放因子（3μg）或低血压激发（需要蓝斑内源性促肾上腺皮质激素释放因子释放）产生的蓝斑激活大大减弱。与对照组相比，急性应激大鼠的促肾上腺皮质激素释放因子剂量反应曲线向右移动。在反复应激的大鼠中，3μg促肾上腺皮质激素释放因子对蓝斑放电的影响也同样减弱。尽管促肾上腺皮质激素释放因子产生的最大效应在这些大鼠中降低，但剂量反应曲线向左移动，表明致敏。低血压挑战对急性应激大鼠无效，但反复应激大鼠的蓝斑放电增加了与匹配对照相似的幅度。反复应激大鼠蓝斑对低血压反应性的恢复可能与促肾上腺皮质激素释放因子的敏感性有关。最后，重复应激方案并没有改变额叶皮层或脑干中促肾上腺皮质激素释放因子受体的亲和力或密度。总之，结果表明，应激史改变了蓝斑突触后水平的促肾上腺皮质激素释放因子神经传递。然而，这些效应并未通过脑干中促肾上腺皮质激素释放因子结合动力学反映出来。压力引起的蓝斑促肾上腺皮质激素释放因子神经递质功能的变化可能在压力相关精神疾病的某些症状中发挥作用。
Spontaneous and stress-evoked discharge of locus coeruleus neurons were characterized in rats with a history of stress. Rats exposed to one or five daily 30-min sessions of footshock were anesthetized with halothane and surgically prepared for locus coeruleus single-unit recording immediately following the last session. Locus coeruleus spontaneous discharge rate and discharge evoked by sciatic nerve stimulation were comparable between acutely and repeatedly stressed rats and controls. In contrast, locus coeruleus activation produced by intracerebroventricular administration of corticotropin-releasing factor (3 mu g) or by hypotensive challenge (which requires endogenous corticotropin-releasing factor release in the locus coeruleus) was greatly attenuated in acutely stressed rats. The corticotropin-releasing factor dose-response curve was shifted to the right in acutely stressed rats compared with controls. In repeatedly stressed rats, the effects of 3 mu g corticotropin-releasing factor on locus coeruleus discharge were similarly diminished. Although the maximum effect produced by corticotropin-releasing factor was decreased in these rats, the dose-response curve was shifted to the left, indicative of sensitization. Hypotensive challenge, which was ineffective in acutely stressed rats, increased locus coeruleus discharge of repeatedly stressed rats by a similar magnitude as in matched controls. The return of locus coeruleus responsiveness to hypotension in repeatedly stressed rats may be related to the sensitization to corticotropin-releasing factor. Finally, the protocol of repeated stress did not alter the affinity or density of corticotropin-releasing factor receptors in either the frontal cortex or brainstem.Taken together, the results suggest that a history of stress alters corticotropin-releasing factor neurotransmission in the locus coeruleus at the postsynaptic level. However, these effects are not reflected by corticotropin-releasing factor binding kinetics in brainstem. Stress-induced changes in corticotropin-releasing factor neurotransmitter function in the locus coeruleus may play a role in certain symptoms of stress-related psychiatric disorders.