Lesions of the Edinger-Westphal nucleus in C57BL/6J mice disrupt ethanol-induced hypothermia and ethanol consumption

Lesions of the Edinger-Westphal nucleus in C57BL/6J mice disrupt ethanol-induced hypothermia and ethanol consumption
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DOI:
10.1111/j.1460-9568.2004.03594.x
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发表时间:
2004-09-01
影响因子:
3.4
通讯作者:
Ryabinin, AE
Ryabinin, AE
中科院分区:
医学3区
文献类型:
--
作者:
Bachtell, RK;Weitemier, AZ;Ryabinin, AE

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Edinger-Westphal核(EW)是一个大脑区域,最近被认为是乙醇的重要新神经靶点。因此,EW是唯一的大脑区域始终显示升高的c-Fos表达后自愿和非自愿乙醇管理。乙醇诱导的c-Fos在EW中的表达已被证明发生在urocortin I阳性神经元中。此外,以前的报告使用几种遗传模型表明,在EW urocortin I系统的差异与乙醇介导的行为,如乙醇诱导的体温过低和乙醇消耗。本研究的目的是使用更直接的策略来确认这些关系。因此,乙醇反应测定电解病变后的EW在雄性C57 BL/6 J小鼠。EW损伤和假手术的动物进行了测试的几个乙醇敏感性的措施和乙醇的消费量在两瓶选择测试。结果表明,EW的病变显着破坏乙醇诱导的低温,而对瞳孔扩张,自发活动或乙醇诱导的镇静没有影响。此外,EW损伤的动物在两瓶选择试验中显示出显著较低的乙醇偏好和消耗的总乙醇剂量。EW损伤的动物也消耗较少的蔗糖比假手术的动物,但没有改变的偏好,蔗糖或奎宁在两瓶的选择测试。这些数据支持先前观察到的遗传相关性EW urocortin I表达和乙醇诱导的体温过低和乙醇消耗。综上所述,研究结果表明,EW可以作为乙醇的传感器,这可以影响乙醇的消费和偏好。
The Edinger-Westphal nucleus (EW) is a brain region that has recently been implicated as an important novel neural target for ethanol. Thus, the EW is the only brain region consistently showing elevated c-Fos expression following both voluntary and involuntary ethanol administration. Ethanol-induced c-Fos expression in the EW has been shown to occur in urocortin I-positive neurons. Moreover, previous reports using several genetic models have demonstrated that differences in the EW urocortin I system are correlated with ethanol-mediated behaviours such as ethanol-induced hypothermia and ethanol consumption. The aim of this study was to confirm these relationships using a more direct strategy. Thus, ethanol responses were measured following electrolytic lesions of the EW in male C57BL/6J mice. Both EW-lesioned and sham-operated animals were tested for several ethanol sensitivity measures and ethanol consumption in a two-bottle choice test. The results show that lesions of the EW significantly disrupted ethanol-induced hypothermia, while having no effect on pupillary dilation, locomotor activity or ethanol-induced sedation. In addition, EW-lesioned animals showed significantly lower ethanol preference and total ethanol dose consumed in the two-bottle choice test. EW-lesioned animals also consumed less sucrose than sham-operated animals, but did not have altered preferences for sucrose or quinine in a two-bottle choice test. These data support previously observed genetic correlations between EW urocortin I expression and both ethanol-induced hypothermia and ethanol consumption. Taken together, the findings suggest that the EW may function as a sensor for ethanol, which can influence ethanol consumption and preference.