Chronic cocaine exposure in the fetal rhesus monkey: consequences for early development of dopamine neurons

Chronic cocaine exposure in the fetal rhesus monkey: consequences for early development of dopamine neurons
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恒河猴胎儿长期接触可卡因:对多巴胺神经元早期发育的影响

DOI:
10.1523/jneurosci.15-11-07330.1995
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发表时间:
1995
影响因子:
1.9
通讯作者:
B. Naylor
B. Naylor
中科院分区:
医学4区
文献类型:
--
作者:
O. Rønnekleiv;B. Naylor

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本文观察了可卡因对恒河猴胚胎含酪氨酸羟化酶(TH)神经元发育的影响。怀孕的猴子用可卡因3毫克/公斤或生理盐水肌肉注射,从妊娠第18天至第40或60天,每天4次。注射后10-20 min,接受该处理的雌性动物血浆中的辅酶A浓度约为800 ng/ml。在剖腹产时,胎儿血液中可卡因的血浆水平为231 +/- 70 ng/ml。应用免疫细胞化学和原位杂交技术对40和60日龄胎脑进行了研究。在妊娠第40天,对照组和可卡因处理的胎猴之间含有TH的神经元的外观没有差异。在两组(N = 3)TH-IR神经元和TH mRNA位于中脑和背侧下丘脑的40天,和纤维投射延伸到发育中的纹状体。此外,在60天的胎儿,TH-IR神经元的分布相似,在两组(N = 5),但TH mRNA的含量,定量原位杂交测定,可卡因治疗后,在黑质(SN)和腹侧被盖区(VTA)减少。这些数据表明,暴露于可卡因在胎儿期不影响TH的发展或其mRNA的表达在妊娠第40天。然而,到第60天,TH mRNA的表达显著降低。后一种效应可以通过可卡因处理的胎儿中多巴胺合成减少来解释。
The effects of cocaine on the development of neurons containing tyrosine hydroxylase (TH) were investigated in fetal rhesus macaques. Pregnant monkeys were treated with cocaine 3 mg/kg or saline i.m., four times a day from day 18 of pregnancy until days 40 or 60. Cocaine concentration in plasma from females thus treated was approximately 800 ng/ml 10–20 min following injection. At the time of C-section, plasma levels of cocaine in fetal blood were 231 +/- 70 ng/ml. The brains from 40 and 60 d old fetuses were examined using immunocytochemistry and in situ hybridization. The appearance of neurons containing TH by day 40 of gestation was not different between control and cocaine-treated fetal monkeys. In both groups (N = 3 each) TH-IR neurons and TH mRNA were located in the mesencephalon and dorsal hypothalamus by day 40, and fiber projections extended to the developing striatum. Also in the day 60 fetuses, the TH-IR neurons were distributed similarly in both groups (N = 5 each), but the TH mRNA content, measured by quantitative in situ hybridization, was reduced in the substantia nigra (SN) and ventral tegmental area (VTA) after cocaine treatment. These data suggest that exposure to cocaine in fetal life does not affect the development of TH or the expression of its mRNA on day 40 of gestation. By day 60, however, the expression of TH mRNA was significantly reduced. This latter effect can be explained by reduced dopamine synthesis in the cocaine-treated fetuses.
DOI: 10.1016/0165-3806(82)90095-5
发表时间: 1982-01-01
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DOI: 10.1037//0735-7044.106.5.837
发表时间: 1992
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DOI: --
发表时间: 1992
期刊: The Journal of pharmacology and experimental therapeutics
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DOI: 10.1016/s0378-4347(00)83384-8
发表时间: 1990
期刊: Journal of chromatography
影响因子: --
作者:
Sandberg,JA;Olsen,GD
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