Prenatal cocaine produces signs of neurodegeneration in the lateral habenula.
Prenatal cocaine produces signs of neurodegeneration in the lateral habenula.
复制标题
产前可卡因会产生外侧缰核神经变性的迹象。
DOI：
10.1016/s0006-8993(99)02181-2
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发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Ellison,G
中科院分区：
文献类型：
--
作者：
Murphy,CA;Ghazi,L;Kokabi,A;Ellison,G
外侧缰核是背侧丘脑的一个核团，通过其主要传出通路--先前已证明，可卡因连续给予成年大鼠数天产生神经变性的外侧缰和FR。因为在怀孕期间暴露于可卡因据报道可能会导致神经行为缺陷，我们研究了是否大鼠胎儿暴露于连续可卡因在妊娠的最后一周将同样表现出选择性神经变性的外侧缰。在妊娠第17天，向母鼠植入两个硅胶小球，每个小球含有溶剂或2种剂量的可卡因（80 mg或55 mg/小球）之一。在外侧缰核和纹状体中计数含有银沉积物的变性神经元。可卡因暴露的幼崽有显着更多的银染色细胞在外侧缰比车辆处理的幼崽，但类似的银染色细胞的数量都存在于所有三个组的纹状体。当在60日龄时对类似处理的溶剂和可卡因暴露动物进行行为测试时，它们在旷场活动、高架十字迷宫上的开臂回避或可卡因的条件性位置偏好的测量上没有差异，尽管线性趋势分析表明可卡因预处理的幼仔在位置偏好测试期间存在一些活动过度。这些结果表明，连续可卡因暴露具有选择性神经毒性作用的缰发育中的胎儿类似于可卡因的成人的影响。
The lateral habenula is a nucleus in the dorsal thalamus that innervates midbrain dopaminergic and serotonergic nuclei via projections through its major efferent pathway, the fasciculus retroflexus (FR). It was previously demonstrated that cocaine administered continuously to adult rats over several days produces neurodegeneration in the lateral habenula and FR. Because exposure to cocaine during pregnancy reportedly can cause neurobehavioral deficits, we examined whether rat fetuses exposed to continuous cocaine during the last week of gestation would similarly demonstrate selective neurodegeneration in the lateral habenula. On day 17 of gestation, dams were implanted with two silicone pellets, each containing either vehicle or one of 2 doses of cocaine (80 mg or 55 mg per pellet). Degenerating neurons containing silver deposits were counted in lateral habenula and in the striatum. Cocaine-exposed pups had significantly more silver-stained cells in the lateral habenula than vehicle-treated pups, but similar numbers of silver-stained cells were present in the striatum of all three groups. When similarly treated vehicle- and cocaine-exposed animals were tested behaviorally at 60 days of age, they did not differ on measures of open field activity, open arm avoidance on the elevated plus-maze or conditioned place preference for cocaine, although a linear trend analysis indicated some hyperactivity of the cocaine-pretreated pups during the place preference test. These results indicate that continuous cocaine exposure has selective neurotoxic effects on the habenula of the developing fetus similar to cocaine's effects in the adult.