Effects of prenatal cocaine exposure on embryonic expression of Sonic hedgehog

Cocaine use by pregnant women may adversely affect development and behavior in the exposed infants. Sonic hedgehog (shh) is a secreted protein that in duces development of many structures in the embryo, including dopaminergic cells in the ventral midbrain, the limb buds, and eyes. Because prenatal co caine exposure has been shown to adversely affect the morphogenesis of thes e and other systems, the present study was undertaken to test the hypothesi s that maternal cocaine treatment would alter shh mRNA expression. Cocaine HCl (60 mg/kg i.p.) was administered to pregnant mice on gestational days 6 -8, the time that immediately precedes the appearance of shh. Control dams received i.p, saline. Embryos from gestational days 9-11 were examined by i n situ hybridization. The temporal and spatial patterns of shh expression w ere indistinguishable between embryos from cocaine- and saline-treated dams . Examination of forebrain, midbrain, and midbody spinal cord coronal secti ons failed to reveal any differences in the dorsoventral and mediolateral l ocalization of shh. The distribution of mRNA for patched (ptc), the membran e receptor for shh, was also indistinguishable between both groups. Chick e mbryos were next used to examine the direct application of cocaine into the developing brain. Shh distribution was similarly unaffected in these chick embryos. These data show that maternal cocaine treatment during early neur al tube development does not significantly alter the expression patterns of shh or ptc mRNA. Thus, congenital defects and behavioral abnormalities ass ociated with maternal cocaine use do not appear to result from altered expr ession of the shh-ptc pathway. Teratology 59:12-19, 1999. (C) 1999 Wiley Li ss, Inc.