Curtis A L, Pavcovich L A, Grigoriadis D E, Valentino R J
Department of Mental Health Sciences, Hahnemann University, Philadelphia, PA 19102-1192, USA.
Neuroscience. 1995 Mar;65(2):541-50. doi: 10.1016/0306-4522(94)00496-r.
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 micrograms) 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 micrograms 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.
对有应激史的大鼠蓝斑神经元的自发放电和应激诱发放电进行了特征描述。每天接受1次或5次、每次30分钟足部电击的大鼠，在最后一次电击后立即用氟烷麻醉，并进行手术准备以记录蓝斑单神经元放电。急性应激和反复应激大鼠与对照组相比，蓝斑自发放电率以及坐骨神经刺激诱发的放电情况相当。相比之下，急性应激大鼠经脑室内注射促肾上腺皮质激素释放因子（3微克）或进行低血压刺激（这需要蓝斑内源性促肾上腺皮质激素释放因子释放）所产生的蓝斑激活作用大大减弱。与对照组相比，急性应激大鼠促肾上腺皮质激素释放因子的剂量反应曲线向右移动。在反复应激的大鼠中，3微克促肾上腺皮质激素释放因子对蓝斑放电的作用同样减弱。虽然这些大鼠中促肾上腺皮质激素释放因子产生的最大效应降低了，但剂量反应曲线向左移动，表明出现了致敏现象。在急性应激大鼠中无效的低血压刺激，使反复应激大鼠的蓝斑放电增加，增加幅度与匹配的对照组相似。反复应激大鼠蓝斑对低血压反应性的恢复可能与对促肾上腺皮质激素释放因子的致敏有关。最后，反复应激方案并未改变额叶皮质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。综上所述，结果表明应激史在突触后水平改变了蓝斑中促肾上腺皮质激素释放因子的神经传递。然而，脑干中促肾上腺皮质激素释放因子的结合动力学并未反映出这些效应。应激诱导的蓝斑中促肾上腺皮质激素释放因子神经递质功能变化可能在应激相关精神障碍的某些症状中起作用。
