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COCAINE INDUCED DISTURBANCES OF MOUSE BRAIN DEVELOPMENT

可卡因引起小鼠大脑发育障碍

基本信息

批准号：
2856546
负责人：
BARRY E KOSOFSKY
金额：
$ 11.85万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-02-01 至 1999-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2856546
关键词：
animal developmental psychology behavior test biomarker brain mapping cocaine developmental neurobiology disease /disorder model dosage embryo /fetus toxicology histogenesis histopathology laboratory mouse neuropsychology placental transfer prenatal growth disorder vibrissae

项目摘要

Between 5-15% of infants born in urban America today have been exposed to cocaine in utero. There is a spectrum of outcomes for "crack kids", with prenatal and postnatal factors influencing the expression of transplacental cocaine effects. Clinical studies have suggested that the single best marker for prenatal cocaine effects, including the postnatal developmental compromise seen in a subset of affected children, is impairment of fetal and postnatal brain growth. We have developed an animal model, in mice, of prenatal cocaine exposure which has allowed us to dissociate the direct effects of cocaine in altering fetal brain development, from the indirect effects associated with cocaine-induced malnutrition. We find that transplacental cocaine exposure independently impairs fetal brain and body growth, results in transient as well as permanent behavioral disturbances in exposed offspring, and results in permanent alterations in neocortical cytoarchitecture. We have proposed experiments to investigate the determinants, correlates and mechanisms underlying these growth, behavioral, and neuropathologic changes. We will use these measures to determine whether cocaine administered during a more restricted gestational period, or at a lower dose, is sufficient to produce alterations in fetal growth and postnatal behavior, and to see whether these features can be dissociated. We propose experiments to identify and quantitate alterations in neocortical structure: a quantitative cytoarchitectonic analysis of the "barrel field" of somatosensory cortex, including measures of cortical thickness, cell density as well as characterization of anatomic markers which reflect alterations in the maturation and precision of anatomic organization of this neocortical region consequent to transplacental cocaine exposure. We propose a series of experiments to map neuronal activation to identify those brain structures and neural systems which are altered in cocaine exposed mice as adults, and which correlate with specific behavioral impairments evident in blocking of second-order aversive conditioning. Information gained from these animal studies should lead to clinical insights regarding gestational exposure to cocaine in humans, fostering improved diagnostics, treatment and prevention of one of the escalating causes of developmental disability in our society.

今天在美国城市出生的婴儿中，有5-15%的婴儿接触过

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A mouse model of transplacental cocaine exposure. Clinical implications for exposed infants and children.

经胎盘可卡因暴露的小鼠模型。

DOI：
发表时间：
1998
期刊：
Annals of the New York Academy of Sciences.
影响因子：
0
作者：
Kosofsky,BE;Wilkins,AS
通讯作者：
Wilkins,AS

Transplacental cocaine exposure. 1: A rodent model.

经胎盘接触可卡因。

DOI：
10.1016/s0892-0362(97)00125-6
发表时间：
1998
期刊：
Neurotoxicology and teratology
影响因子：
2.9
作者：
Wilkins,AS;Genova,LM;Posten,W;Kosofsky,BE
通讯作者：
Kosofsky,BE

Transplacental cocaine exposure. 3: Mechanisms underlying altered brain development.

经胎盘接触可卡因。

DOI：
10.1016/s0892-0362(97)00128-1
发表时间：
1998
期刊：
Neurotoxicology and teratology
影响因子：
2.9
作者：
Wilkins,AS;Marota,JJ;Tabit,E;Kosofsky,BE
通讯作者：
Kosofsky,BE

Preadolescent methylphenidate versus cocaine treatment differ in the expression of cocaine-induced locomotor sensitization during adolescence and adulthood.

青春期前哌醋甲酯与可卡因治疗在青春期和成年期可卡因诱导的运动敏化的表达方面存在差异。

DOI：
10.1016/j.biopsych.2006.03.034
发表时间：
2006
期刊：
Biological psychiatry
影响因子：
10.6
作者：
Guerriero,RejeanM;Hayes,MargaretM;Dhaliwal,SharonK;Ren,Jia-Qian;Kosofsky,BarryE
通讯作者：
Kosofsky,BarryE

Transplacental cocaine exposure. 2: Effects of cocaine dose and gestational timing.

经胎盘接触可卡因。