School of Psychology, University of New South Wales, Sydney, New South Wales 2052, Australia.
J Neurosci. 2011 Oct 5;31(40):14151-7. doi: 10.1523/JNEUROSCI.3014-11.2011.
Systemic fibroblast growth factor 2 (FGF2) has been shown to enhance extinction of conditioned fear and attenuate subsequent relapse in developing rats. However, it is not clear whether FGF2 has the same effect in adult rats, and furthermore, the neuroanatomical locus of the effect of FGF2 on extinction is unknown. These experiments examined the effect of 200 ng of FGF2, infused bilaterally into the basolateral complex of the amygdala (BLA), on the extinction of conditioned fear in adult rats. Experiment 1 confirmed that intra-BLA FGF2 significantly enhances extinction recall in adult rats, and extinction training is necessary for this effect to occur (FGF2 did not reduce conditioned freezing in the absence of extinction training). In Experiments 2 and 3, vehicle-treated rats were given four times the amount of extinction training as FGF2-treated rats to equate the strength of extinction between groups. In Experiment 2, rats were tested in both the extinction training context and the conditioning context to examine the effect of FGF2 on renewal of fear. In Experiment 3, the FGF2-treated rats and one-half of the vehicle-treated rats received a single unsignaled shock before test to examine the effect of FGF2 on reinstatement of fear. In both procedures, FGF2 administered immediately after extinction training significantly reduced relapse at test. These results support a growing body of evidence that FGF2 may be a potentially useful pharmacological adjunct to exposure-based therapies for anxiety disorders.
系统纤维母细胞生长因子 2(FGF2)已被证明可增强条件性恐惧的消退,并减轻发展中大鼠随后的复发。然而,目前尚不清楚 FGF2 在成年大鼠中是否具有相同的作用,此外,FGF2 对消退的神经解剖学位置尚不清楚。这些实验研究了双侧注入杏仁核基底外侧复合体(BLA)的 200ng FGF2 对成年大鼠条件性恐惧消退的影响。实验 1 证实,BLA 内的 FGF2 显著增强了成年大鼠的消退回忆,并且这种作用的发生需要进行消退训练(如果没有进行消退训练,FGF2 不会减少条件性冻结)。在实验 2 和 3 中,给予载体处理的大鼠比 FGF2 处理的大鼠多进行四次的消退训练,以使两组之间的消退强度相等。在实验 2 中,大鼠在消退训练环境和条件环境中进行测试,以研究 FGF2 对恐惧更新的影响。在实验 3 中,FGF2 处理的大鼠和一半的载体处理的大鼠在测试前接受单次未标记的休克,以研究 FGF2 对恐惧恢复的影响。在这两种程序中,FGF2 在消退训练后立即给予,可显著减少测试中的复发。这些结果支持越来越多的证据表明,FGF2 可能是暴露疗法治疗焦虑症的一种潜在有用的药理学辅助手段。