Koob G F, Heinrichs S C, Pich E M, Menzaghi F, Baldwin H, Miczek K, Britton K T
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Ciba Found Symp. 1993;172:277-89; discussion 290-5. doi: 10.1002/9780470514368.ch14.
Corticotropin-releasing factor (CRF), when administered directly into the CNS, can have activating properties on behaviour and can enhance behavioural responses to stress. CRF injected intraventricularly produces a dose-dependent increase in locomotor activity and increased responsiveness to an acoustic startle stimulus. However, this profile of activation changes to enhanced suppression of behaviour in stressful situations and includes increased freezing, increased conditioned suppression, increased conflict, decreased feeding and decreased behaviour in a novel open field. These effects of CRF are independent of the pituitary-adrenal axis and can be reversed by the CRF antagonist alpha-helical CRF(9-41). More importantly, the CRF antagonist can also reverse many behavioural responses to stressors. alpha-Helical CRF(9-41) reverses stress-induced fighting behaviour, stress-induced freezing, stress-induced suppression of feeding, stress-induced decreases in exploration of an elevated plus maze, fear-potentiated startle and the development of conditioned suppression. Intracerebral microinjections suggest that the amygdala may be an important site for the anti-stress effects of alpha-helical CRF(9-41). These results suggest that endogenous CRF systems in the CNS may have a role in mediating behavioural responses to stress and further suggest that CRF in the brain may function as a fundamental behavioural activating system. This CRF system may be particularly important in situations where an organism must mobilize not only the pituitary-adrenal system but also the CNS in response to environmental challenge.
促肾上腺皮质激素释放因子（CRF）直接注入中枢神经系统时，可对行为产生激活作用，并能增强对应激的行为反应。脑室内注射CRF会使运动活动呈剂量依赖性增加，并增强对听觉惊吓刺激的反应性。然而，这种激活模式在应激情况下会转变为对行为的增强抑制，包括僵住增加、条件性抑制增加、冲突增加、进食减少以及在新的开阔场地中的行为减少。CRF的这些作用独立于垂体 - 肾上腺轴，并且可被CRF拮抗剂α - 螺旋CRF（9 - 41）逆转。更重要的是，CRF拮抗剂还能逆转对应激源的许多行为反应。α - 螺旋CRF（9 - 41）可逆转应激诱导的打斗行为、应激诱导的僵住、应激诱导的进食抑制、应激诱导的高架十字迷宫探索减少、恐惧增强的惊吓以及条件性抑制的发展。脑内微注射表明杏仁核可能是α - 螺旋CRF（9 - 41）抗应激作用的重要部位。这些结果表明中枢神经系统中的内源性CRF系统可能在介导对应激的行为反应中起作用，并且进一步表明脑中的CRF可能作为一个基本的行为激活系统发挥作用。这种CRF系统在生物体不仅必须动员垂体 - 肾上腺系统而且还必须动员中枢神经系统以应对环境挑战的情况下可能特别重要。
