Valentino R J, Foote S L, Page M E
Department of Mental Health Sciences, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
Ann N Y Acad Sci. 1993 Oct 29;697:173-88. doi: 10.1111/j.1749-6632.1993.tb49931.x.
Anatomic and electrophysiologic studies have provided evidence that CRF meets some of the criteria as a neurotransmitter in the noradrenergic nucleus, the locus coeruleus (LC), although some of the criteria have yet to be satisfied. Thus, immunohistochemical findings suggest that CRF innervates the LC, but this must be confirmed at the ultrastructural level. CRF alters discharge activity of LC neurons and these effects are mimicked by some stressors. Moreover, the effects of hemodynamic stress on LC activity are prevented by a CRF antagonist. However, it has not been demonstrated that stimulation of CRF neurons that project to the LC activates the LC or that the effects of such stimulation are prevented by a CRF antagonist. The role of CRF in LC activation by stressors other than hemodynamic stress needs to be determined. It could be predicted that the effects of CRF neurotransmission in the LC during stress would enhance information processing concerning the stressor or stimuli related to the stressor by LC target neurons. One consequence of this appears to be increased arousal. Although this may be adaptive in the response to an acute challenge, it could be predicted that chronic CRF release in the LC would result in persistently elevated LC discharge and norepinephrine release in targets. This could be associated with hyperarousal and loss of selective attention as occurs in certain psychiatric diseases. Manipulation of endogenous CRF systems may be a novel way in which to treat psychiatric diseases characterized by these maladaptive effects.
解剖学和电生理学研究已经提供证据表明，促肾上腺皮质激素释放因子（CRF）符合作为去甲肾上腺素能核团蓝斑（LC）中神经递质的部分标准，尽管还有一些标准尚未得到满足。因此，免疫组织化学结果表明CRF支配蓝斑，但这必须在超微结构水平上得到证实。CRF改变蓝斑神经元的放电活动，并且这些效应被一些应激源模拟。此外，血流动力学应激对蓝斑活动的影响可被CRF拮抗剂阻断。然而，尚未证实投射至蓝斑的CRF神经元的刺激会激活蓝斑，或者这种刺激的效应可被CRF拮抗剂阻断。CRF在除血流动力学应激之外的应激源激活蓝斑中的作用有待确定。可以预测，应激期间CRF在蓝斑中的神经传递效应会增强蓝斑靶神经元关于应激源或与应激源相关刺激的信息处理。这一情况的一个后果似乎是觉醒增加。虽然这在应对急性挑战时可能具有适应性，但可以预测，蓝斑中慢性CRF释放会导致蓝斑放电持续升高以及靶组织中去甲肾上腺素释放增加。这可能与某些精神疾病中出现的过度觉醒和选择性注意力丧失有关。操纵内源性CRF系统可能是治疗以这些适应不良效应为特征的精神疾病的一种新方法。
