产前接触可卡因对胎儿神经元的危害

佚名

尽管20世纪80年代有关“可卡婴”（备注1）的报道被严重夸大，但母体怀孕阶段接触可卡因确实可以引起后代轻微的先天性功能障碍——注意力缺陷，学习障碍和情感问题等。

美国范德比大学肯尼迪人类发展研究中心(*)的研究者们在产前可卡因接触对胎儿行为、神经影响方面有着更为深入的理解。在最新发表在《Journal  of  Neuroscience》杂志上的文章中，Gregg  Stanwood和Pat  Levitt通过对兔子的研究，发现产前可卡因接触会引起某些脑细胞多巴胺受体的长期移位，从而妨碍了它们正常功能的行使。

更为具体地说，研究者在兔子模型中发现多巴胺D1受体（dopamine  D1  receptor）尽管在神经元中的表达总量没有明显变化，但蛋白分布却发生了显著变化：由细胞表面跑进了细胞内部。

如果这个在人类中也有同样的规律，“这将有助于我们去帮助有困难的孩子。”因为可卡因接触似乎可以改变D1受体的分布，Stanwood建议研究者开发出一种方法让受体“迷途知返”。

“现在还没有学者得到人相关的数据，”  Stanwood说道，“接下去的研究将会非常关键。”

英文词汇：

*Vanderbilt  Kennedy  Center  for  Research  on  Human  Development

备注1：crack  baby；患有某种先天性功能不全的婴儿,因孕妇吸食可卡因而感染的。

英文原文：

Cocaine use during pregnancy has lasting cellular effects

A new study has found that though the "crack baby" hysteria of the 1980s was greatly exaggerated, using cocaine during pregnancy can nonetheless cause subtle but disabling cognitive impairments in kids.

These impairments include attention deficits, learning disabilities and emotional problems.

The study was conducted by researchers at the Vanderbilt Kennedy Center for Research on Human Development.

Researchers Gregg Stanwood, Ph.D., and Pat Levitt, Ph.D., in a study on rabbits, found that prenatal cocaine exposure causes a long lasting displacement of dopamine receptors in certain brain cells, which alters their ability to function normally.

Dr Stanwood said that though the "crack baby" hysteria was "sort of overblown", using high levels of cocaine - usually coupled with the abuse of other drugs - can lead to premature labour, preterm birth and low birth weight.

"The hysteria surrounding the 'crack baby' was sort of overblown," said Stanwood, research assistant professor of Pharmacology and lead author on the study.

He added that even though children of women who have used low recreational doses of cocaine seem to be "normal" at birth, they tend to develop deficits in their cognitive and emotional development as they grow older.

"But in women who have abused relatively low recreational doses of cocaine, it is actually very hard to distinguish those children at birth from children born to anyone else. However, as those children age, they do develop deficits in their cognitive and emotional development," he said.

These children often exhibit attention and arousal problems, similar to children with attention deficit hyperactivity disorder (ADHD). However, the standard treatments for ADHD -- Ritalin and other stimulants -- are not always effective in these children.

In a previous study, the researchers had found that exposure to low levels of intravenous cocaine during a very short window of time during gestation - equivalent to the late first trimester and early second trimester in humans - caused specific alterations in brain circuits that use the neurotransmitter dopamine that is involved in regulating the formation of cortical circuitry.

Additionally, these cocaine-exposed offspring showed attention problems as well as insensitivity to stimulants like amphetamine, suggesting that cocaine exposure had altered the development of the dopamine pathways in the brain.

"In collaboration with Dr. Eitan Friedman of the City University of New York, we had previously shown a decrease in signalling of a particular receptor protein, the dopamine D1 receptor. We know that this receptor is involved in regulating the formation of cortical circuitry. It's also involved in the behavioural effects of amphetamines and cocaine," Dr Stanwood.

As a part of the present study, Dr Stanwood examined the levels of D1 receptor in brain cells taken from "teenage" rabbits that were exposed to cocaine during that short, sensitive prenatal period, and found that though cocaine exposure did not alter the total amount of D1 receptor produced in the brain, however, there was a dramatic alteration in the location of the protein within the cell.

D1 receptors are normally found at the cell surface, but neurons from the cocaine-exposed animals showed the receptor was predominantly sequestered inside the cells.

The effect, which "appears permanent" the researchers state, implies that cocaine exposure during a brief, sensitive period of neural development can lead to long-lasting effects at the cellular level.

This change also altered the growth of neuronal processes, suggesting that the altered D1 receptor trafficking may underlie the changes in neuronal architecture and behaviour.

The researchers insisted that though this effect has not yet been assessed in cocaine-exposed children, the findings gives them a place to start looking.

"Neither we nor anyone else has yet identified whether this mechanism occurs in the human population so that is a critical next step," Stanwood said.

The study is published in a recent issue of the Journal of Neuroscience.