The Ontogeny of Immediate Early Gene 
Response to Cocaine: A Molecular 
Analysis of the Effects of Cocaine on 
Developing Rat Brain 
Barry E. Kosofsky and Steven E. Hyman 
EPIDEMIOLOGY 
Current estimates suggest that between 13 and 17 percent of infants born 
in urban hospitals in the United States have been exposed to cocaine in 
utero (Frank et al. 1988). Multivariate analysis has shown that mothers 
who abuse cocaine during gestation have infants with a 93-g lower birth 
weight, a .17-centimeter decrement in length, and a .43-centimeter smaller 
head circumference (Zuckerman et al. 1989). The dramatic decrease in 
head size is a further indication of in utero effects of maternal cocaine on the 
developing brain. Drug-induced changes in brain development are likely to 
account for the hyperreflexia, increased irritability, alterations in tone and 
coordination, and developmental delay, including fine motor and visual motor 
skills, seen in some infants exposed to cocaine in utero (Kosofsky 1991). 
CENTRAL NERVOUS SYSTEM MATURATION 
Clinical data suggest that infants exposed to cocaine only during the first 
trimester of gestation are normal size at birth but show a statistically significant 
compromise of the Neonatal Behavioral Assessment Scale (Brazelton), with 
poor orienting, poor motor ability, and abnormal reflexes (Chasnoff et al. 1989). 
The implications are that the window of vulnerability to cocaine for developing 
brain may begin early in gestation and that the toxicity ultimately manifested 
may be dependent on the time of fetal exposure. The protracted timetable 
of central nervous system (CNS) maturation confers a continuum of biologic 
vulnerability to developing brain. Moreover, the developmental consequences 
of a toxic CNS insult relate critically to the period during which the fetus is 
exposed to drugs (Evrard et al. 1989). 
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