Corticotropin-releasing factor and noradrenergic signalling exert reciprocal control over startle reactivity.
Corticotropin-releasing factor and noradrenergic signalling exert reciprocal control over startle reactivity.
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DOI：
10.1017/s1461145710001409
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Risbrough VB
中科院分区：
文献类型：
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作者：
Gresack JE;Risbrough VB
促肾上腺皮质激素释放因子（CRF）和去甲肾上腺素（NE）水平在创伤后应激障碍中改变，可能与这些患者的过度觉醒症状有关，包括过度惊吓。在动物中，这两个系统的激活调节焦虑行为，包括惊吓可塑性，但它是未知的，如果他们发挥他们的行动正交或依赖。我们测试了这样的假设，即NE受体激活是CRF对惊吓的影响所必需的，而CRF 1受体激活是NE对惊吓的影响所必需的。本研究检测了：1）α2受体激动剂可乐定（0.18 mg/kg，ip），α1受体拮抗剂哌唑嗪（0.8 mg/kg）和β1/2拮抗剂普萘洛尔（0.8、8.0 mg/kg）oCRF预处理-（0.6 nmol）引起惊吓反应性增加和PPI中断; α2受体拮抗剂阿替美唑（1-30 mg/kg）和α1受体激动剂cirazoline（0.025-1.0 mg/kg）对惊恐反应的影响; oCRF显著增加惊吓和降低PPI。可乐定或哌唑嗪预处理，而不是普萘洛尔，阻断oCRF诱导的惊吓增加，但对oCRF诱导的PPI中断没有影响。阿替美唑治疗增加惊吓，这是部分衰减的CRF 1拮抗剂预处理。西拉唑啉治疗没有增加惊吓。这些结果表明，CRF对惊吓的调节，而不是PPI，需要激活α1肾上腺素能受体，而CRF 1激活也有助于NE对惊吓的调节。这些数据支持一个双向模型的CRF-NE调制的应激反应，并建议，这两个系统必须被激活，以诱导应激反应的惊吓反应。
Corticotropin-releasing factor (CRF) and norepinephrine (NE) levels are altered in post-traumatic stress disorder and may be related to symptoms of hyperarousal, including exaggerated startle, in these patients. In animals, activation of both systems modulates anxiety behaviors including startle plasticity, however it is unknown if they exert their actions orthogonally or dependently. We tested the hypothesis that NE receptor activation is required for CRF effects on startle and that CRF1 receptor activation is required for NE effects on startle. The study examined the effects of: 1) α2 agonist clonidine (0.18 mg/kg, ip), α1 antagonist prazosin (0.8 mg/kg), and β1/2 antagonist propranolol (0.8, 8.0 mg/kg) pretreatment on oCRF- (0.6 nmol) induced increases in startle reactivity and PPI disruptions; 2) α2 antagonist atipamezole (1–30 mg/kg) and α1 agonist cirazoline (0.025–1.0 mg/kg) treatment on startle; 3) CRF1 antagonist (antalarmin, 14 mg/kg) pretreatment on atipamezole- (10.0 mg/kg) induced increases in startle. oCRF robustly increased startle and reduced PPI. Pretreatment with clonidine or prazosin, but not propranolol, blocked oCRF-induced increases in startle but had no effect on oCRF-induced disruptions in PPI. Atipamezole treatment increased startle, which was partially attenuated by CRF1 antagonist pretreatment. Cirazoline treatment did not increase startle. These findings suggest that CRF modulation of startle, but not PPI, requires activation of α1 adrenergic receptors, while CRF1 activation also contributes to NE modulation of startle. These data support a bi-directional model of CRF-NE modulation of stress responses and suggest that both systems must be activated to induce stress effects on startle reactivity.