The effect of prenatal cocaine on the anatomical development of the st
riatum was examined. The distribution and density of dopaminergic inne
rvation of the striatum of animals exposed to cocaine during the secon
d and third week of gestation was not noticeably different from prenat
ally saline-injected or untreated controls at any age. The patch/matri
x organization of the striatum also appeared unaltered: neurons exhibi
ting dense substance P staining were localized to patches that overlap
ped dopamine terminal patches early in development, and enkephalin- an
d calbindin-immunoreactive neurons were found segregated to the matrix
. Histochemical staining for acetylcholinesterase and NADPH diaphorase
also revealed no differences between prenatally cocaine-treated and c
ontrol brains. Whereas prenatal cocaine treatment failed to modify the
basic compartmental organization of the striatum, it did lead to a hy
perinnervation of serotonin-immunoreactive fibers which developed slow
ly after birth. Thus prenatal exposure to cocaine is capable of alteri
ng the ingrowth of serotonergic projections to the striatum while prod
ucing no change in the organization of neurons intrinsic to the striat
um.