Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches
Neurotoxic effects of DSP-4 on the central noradrenergic system in male zebra finches
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DOI：
10.1016/j.bbr.2007.11.004
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发表时间：
2008-04-09
影响因子：
2.7
通讯作者：
Harding, Cheryl F.
中科院分区：
文献类型：
--
作者：
Waterman, Susanna A.;Harding, Cheryl F.
当全身给药时，去甲肾上腺素能神经毒素 N-(2-氯乙基)-N'-etliyl-2-bromobenzylamine (DSP-4) 似乎会靶向源自蓝斑的去甲肾上腺素能神经支配，导致去甲肾上腺素能功能长期减弱。在鸣禽中，DSP-4 治疗降低了雄性对雌性的歌唱以及雌性对雄性歌曲的求偶反应。然而，鸣禽的 DSP-4 治疗并没有像哺乳动物那样降低大脑 NE 功能的程度。目前的研究有两个目标：确定间隔 10 天的两次 DSP-4 治疗是否会导致雄性斑胸草雀的去甲肾上腺素能功能显着下降，并确定是否像其他物种一样，中脑和皮质区域的去甲肾上腺素能神经支配会受到严重影响，而下丘脑区域则不受影响。多巴胺-β-羟化酶免疫反应性 (DBH-ir) 在 13 个大脑区域（5 个发声控制核、1 个听觉核、2 个下丘脑核和 5 个在对照中表现出高 DBH 标记的其他区域）进行了定量。 20 天内，DSP-4 治疗显着减少了蓝斑和腹侧蓝斑下层中 DBH-ir 细胞的数量。与之前的研究不同，DBH 标记描绘了五个发声控制核中的四个和所有听觉核。正如预期的那样，DSP-4 治疗显着降低了中脑和端脑所有检查区域的 DBH 标记，而没有显着影响下丘脑区域的 DBH-ir。这种双重治疗方案似乎比通常使用的单一治疗更有效地降低鸣禽的去甲肾上腺素能功能。 (C) 2007 Elsevier B.V. 保留所有权利。
When administered systemically, the noradrenergic neurotoxin N-(2-chloroethyl)-N'-etliyl-2-bromobenzylamine (DSP-4) appears to target the noradrenergic innervation originating in the locus coeruleus causing long-term decrements in noradrenergic function. In songbirds, DSP-4-treatment decreased female-directed singing by males and copulation solicitation responses of females to male songs. However, DSP-4 treatment in songbirds did not lower measures of NE function in the brain to the same extent as it does in mammals. The current study had two goals: determining if two DSP-4 treatments 10 days apart would cause significant decrements in noradrenergic function in male zebra finches and determining if, as in other species, the noradrenergic innervation of midbrain and cortical areas would be profoundly affected while hypothalamic areas were spared. Dopamine-beta-hydroxylase immunoreactivity (DBH-ir) was quantified in thirteen brain regions (five vocal control nuclei, one auditory nucleus, two hypothalamic nuclei, and five additional areas that demonstrated high DBH labeling in controls). Within 20 days, DSP-4 treatment profoundly reduced the number of DBH-ir cells in both the locus coeruleus and ventral subcoeruleus. Unlike a previous study, DBH labeling delineated four out of five vocal control nuclei and ail auditory nucleus. As expected, DSP-4 treatment significantly decreased DBH labeling in all areas examined in the mesencephalon and telencephalon without significantly affecting DBH-ir in hypothalamic areas. This double treatment regime appears to be much more effective in decreasing noradrenergic function in songbirds than the single treatment typically used. (C) 2007 Elsevier B.V. All rights reserved.