Erb Suzanne, Funk Douglas, Lê Anh Dzung
Centre for the Neurobiology of Stress, Departments of Life Science and Psychology, University of Toronto at Scarborough, 1265 Military Trail, Toronto, Ont., Canada M1C 1A4.
Neurosci Lett. 2005 Aug 5;383(3):209-14. doi: 10.1016/j.neulet.2005.04.013. Epub 2005 Apr 26.
There is evidence that cocaine pre-exposure produces changes in the responsivity of central corticotropin-releasing factor (CRF) systems and that these systems mediate some of the drug-related behavioural effects of acute stressors. The present experiment was conducted to assess the effects of repeated cocaine exposure on CRF-induced neuronal activation within two regions of the extended amygdala, the central nucleus of the amygdala (CeA) and lateral bed nucleus of the stria terminalis (BNST). In addition, CRF-induced neuronal activation was compared with CRF-induced locomotor activity. Rats were injected for 7 days with cocaine (days 1 and 7 in test chambers; days 2-6 in homecages) or saline. After 10 drug-free days, locomotor responsiveness to intracerebroventricular (i.c.v.) injections of CRF and Vehicle was assessed over 2-h test periods. Twenty-four to 48 h following testing for locomotor activity, animals were injected with either CRF or Vehicle, 30 min before being sacrificed. Subsequently, the brains were processed by in situ hybridization for c-fos mRNA, a widely used marker of neuronal activation, in the CeA and BNST. In CeA, i.c.v. CRF enhanced the expression of c-fos mRNA in cocaine, but not saline, pre-exposed animals; in the same animals, i.c.v. CRF resulted in enhanced locomotor activity in cocaine, but not saline, pre-exposed animals. The results demonstrate that repeated exposure to cocaine changes the neuronal response to CRF in the CeA; furthermore, they suggest that these changes in the CeA could potentially be of functional significance in the effects of repeated cocaine exposure on CRF-induced locomotor activity.
有证据表明，预先接触可卡因会使中枢促肾上腺皮质激素释放因子（CRF）系统的反应性发生变化，并且这些系统介导了急性应激源的一些与药物相关的行为效应。本实验旨在评估重复接触可卡因对扩展杏仁核的两个区域——杏仁核中央核（CeA）和终纹床核外侧部（BNST）内CRF诱导的神经元激活的影响。此外，还将CRF诱导的神经元激活与CRF诱导的运动活动进行了比较。大鼠连续7天注射可卡因（第1天和第7天在测试箱中；第2 - 6天在饲养笼中）或生理盐水。在10天无药物期后，在2小时的测试期内评估对脑室内（i.c.v.）注射CRF和赋形剂的运动反应性。在测试运动活动24至48小时后，在处死动物前30分钟给动物注射CRF或赋形剂。随后，通过原位杂交检测CeA和BNST中c-fos mRNA的表达，c-fos mRNA是一种广泛使用的神经元激活标记物。在CeA中，i.c.v. CRF增强了预先接触可卡因而非生理盐水的动物中c-fos mRNA的表达；在相同的动物中，i.c.v. CRF导致预先接触可卡因而非生理盐水的动物运动活动增强。结果表明，重复接触可卡因会改变CeA中神经元对CRF的反应；此外，它们表明CeA中的这些变化可能对重复接触可卡因对CRF诱导的运动活动的影响具有潜在的功能意义。
