Butler P D, Weiss J M, Stout J C, Nemeroff C B
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710.
J Neurosci. 1990 Jan;10(1):176-83. doi: 10.1523/JNEUROSCI.10-01-00176.1990.
The present series of experiments tested the hypothesis that the behavioral activating and anxiogenic effects produced by intraventricular administration of corticotropin-releasing factor (CRF) may be mediated by noradrenergic neurons in the brain-stem locus coeruleus (LC). Results showed that infusion of CRF into the LC (100 ng) significantly increased nonambulatory spontaneous motor activity measured in photocell cages; ambulatory (i.e., locomotor) activity was not altered. In the modified Porsolt swim test, which examines arousal and agitation in a stressful situation, significant behavioral activation (i.e., decreased floating) was seen following infusion of CRF (10 ng) into the LC; a 500 ng dose of CRF was necessary to produce similar effects following infusion into the lateral ventricle. The results of these 2 tests suggest that the behavioral activating effects of CRF in the LC may be related to arousing or stress-related effects, rather than to increased locomotor activity per se. Anxiogenic activity was assessed in animals placed in an open field containing a small, darkened compartment. Infusion or CRF into the LC (1-100 ng) significantly increased the time spent in the compartment and decreased the amount of time spent exploring the outside of the compartment or venturing into the inner squares of the open field, all indices of anxiogenic behavior. Biochemical studies showed that bilateral infusion of CRF into the LC produced significant increases in the concentration of the norepinephrine metabolite 3,4-dihydroxyphenylglycol in such forebrain projection areas of the LC as the amygdala and posterior hypothalamus. These data, taken together, suggest that CRF produces its behavioral activating and anxiogenic effects, at least in part, by increasing the activity of LC noradrenergic neurons.
脑室内注射促肾上腺皮质激素释放因子（CRF）所产生的行为激活和致焦虑效应可能由脑干蓝斑（LC）中的去甲肾上腺素能神经元介导。结果显示，向LC中注入CRF（100 ng）可显著增加在光电管笼中测量的非走动性自发运动活动；走动性（即运动性）活动未改变。在改良的波索尔特游泳试验中，该试验用于检测应激状态下的觉醒和激动情况，向LC中注入CRF（10 ng）后出现了显著的行为激活（即漂浮减少）；向侧脑室注入500 ng剂量的CRF才能产生类似效果。这两项试验的结果表明，CRF在LC中的行为激活效应可能与觉醒或应激相关效应有关，而非与运动活动本身的增加有关。在置于含有一个小的黑暗隔室的旷场中的动物身上评估致焦虑活性。向LC中注入CRF（1 - 100 ng）显著增加了在隔室中花费的时间，并减少了探索隔室外侧或进入旷场内部方格的时间，所有这些都是致焦虑行为的指标。生化研究表明，向LC双侧注入CRF会使LC在前脑投射区域（如杏仁核和下丘脑后部）中的去甲肾上腺素代谢物3,4 - 二羟基苯乙二醇的浓度显著增加。综合这些数据表明，CRF至少部分地通过增加LC去甲肾上腺素能神经元的活性来产生其行为激活和致焦虑效应。
