Frankland P W, Josselyn S A, Bradwejn J, Vaccarino F J, Yeomans J S
Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 1A1.
J Neurosci. 1997 Mar 1;17(5):1838-47. doi: 10.1523/JNEUROSCI.17-05-01838.1997.
The acoustic startle reflex is a sensitive index of "anxiety" and "fear." Potentiation of startle by conditioned and unconditioned fear stimuli appears to be mediated by the amygdala. CholecystokininB (CCKB) agonists increase "anxiety" in laboratory animals and induce "panic" in humans. Here, we investigate the role CCKB receptor-mediated mechanisms in the amygdala in the potentiation of startle. First, intra-amygdala infusions of the CCKB receptor agonist pentagastrin (0, 0.01, 0.1, 1, and 10 nM) produced a dose-related potentiation of acoustic startle responses. At the highest dose, startle amplitudes were increased up to 90% above preinfusion baseline levels. Second, similar infusions of pentagastrin had no effect on locomotor activity over the same time course, showing that increases in startle responsivity after infusions of pentagastrin are not attributable to nonspecific changes in motor activity. Third, infusions of similar doses of pentagastrin into the striatum or nucleus accumbens did not potentiate startle responses. Fourth, pretreatment with the CCKB receptor antagonist L-365,260 (0.1 mg/kg, i.p.) attenuated the potentiation of startle produced by intra-amygdala infusions of pentagastrin. Finally, intra-amygdala infusion of the CCKB receptor-selective antagonist PD-135158 (10 micro;g) blocked the potentiation of startle produced by i.c.v. infusions of pentagastrin, suggesting that i.c.v. infusions of pentagastrin potentiate startle responses via activation of amygdala CCKB receptors. These results show that amygdala CCKB receptor-mediated mechanisms are involved in the potentiation of acoustic startle responses.
听觉惊吓反射是“焦虑”和“恐惧”的敏感指标。条件性和非条件性恐惧刺激对惊吓的增强作用似乎是由杏仁核介导的。胆囊收缩素B（CCKB）激动剂会增加实验动物的“焦虑”并在人类中诱发“惊恐”。在此，我们研究杏仁核中CCKB受体介导的机制在惊吓增强中的作用。首先，向杏仁核内注射CCKB受体激动剂五肽胃泌素（0、0.01、0.1、1和10 nM）会产生与剂量相关的听觉惊吓反应增强。在最高剂量时，惊吓幅度比注射前基线水平增加了90%。其次，在相同时间进程内，类似剂量的五肽胃泌素注射对运动活动没有影响，这表明注射五肽胃泌素后惊吓反应性的增加并非归因于运动活动的非特异性变化。第三，向纹状体或伏隔核注射类似剂量的五肽胃泌素不会增强惊吓反应。第四，用CCKB受体拮抗剂L-365,260（0.1 mg/kg，腹腔注射）预处理可减弱杏仁核内注射五肽胃泌素所产生的惊吓增强作用。最后，向杏仁核内注射CCKB受体选择性拮抗剂PD-135158（10μg）可阻断脑室内注射五肽胃泌素所产生的惊吓增强作用，这表明脑室内注射五肽胃泌素通过激活杏仁核CCKB受体增强惊吓反应。这些结果表明，杏仁核CCKB受体介导的机制参与了听觉惊吓反应的增强。
