Menzaghi F, Heinrichs S C, Merlo-Pich E, Tilders F J, Koob G F
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037.
Neurosci Lett. 1994 Feb 28;168(1-2):139-42. doi: 10.1016/0304-3940(94)90435-9.
The purpose of this experiment was to investigate whether endogenous corticotropin-releasing factor (CRF) within the paraventricular nucleus of the hypothalamus (PVN) is involved in the alteration of locomotor activity related to a novel, presumably stressful, environment in rats. Impairment of the function of CRF-containing neurons was effected by immunotargeting ricin A chain toxin to these cells with a monoclonal antibody to CRF (CRF-MAb/toxins). CRF-MAb/toxins administered into the PVN 2 weeks prior to testing produced an increase in locomotor activity during exposure to novel environment photocell cages. This behavioral activation was maintained throughout the 120 min experimental session, but was not present when the rats where introduced to the same photocell cages after extensive habituation. These results suggest that the effect induced by CRF-MAb/toxin treatment was related to the exploration of the novel environment, and was not due to a generalized locomotor hyperactivity. This effect was accompanied by a 53% and 61% CRF decrease in the hypothalamus and the median eminence, respectively. Injection of CRF-MAb/toxins into the ventromedial nucleus of the hypothalamus did not modify the locomotor activity in either unfamiliar or familiar conditions. These data suggest that CRF neurons within the PVN may participate not only in the activation of the pituitary adrenal axis associated with stressors but also as physiological mediators of the behavioral responses to stress.
本实验的目的是研究下丘脑室旁核（PVN）内的内源性促肾上腺皮质激素释放因子（CRF）是否参与大鼠在新的、可能有压力的环境中与运动活动改变相关的过程。通过用抗CRF单克隆抗体（CRF-MAb/毒素）将蓖麻毒素A链靶向这些含CRF的神经元来实现对其功能的损害。在测试前2周将CRF-MAb/毒素注入PVN，在暴露于新环境光电池笼期间会使运动活动增加。这种行为激活在整个120分钟的实验过程中持续存在，但当大鼠在广泛适应后被引入相同的光电池笼时则不存在。这些结果表明，CRF-MAb/毒素处理诱导的效应与对新环境的探索有关，而不是由于普遍的运动活动亢进。这种效应伴随着下丘脑和正中隆起中CRF分别下降53%和61%。将CRF-MAb/毒素注入下丘脑腹内侧核在不熟悉或熟悉的条件下均未改变运动活动。这些数据表明，PVN内的CRF神经元不仅可能参与与应激源相关的垂体-肾上腺轴的激活，还可能作为对应激行为反应的生理介质。
