PERINATAL COCAINE EXPOSURE ALTERS SIGMA BINDING-SITE DENSITY IN THE PLACENTA

Fetal cocaine exposure in utero leads to direct neurotoxic effects and indirect consequences secondary to intrauterine growth retardation. R egulation of hormone and neurotransmitter receptors in the placenta by cocaine may contribute to the spectrum of adverse effects associated with cocaine use during pregnancy. Previous studies have demonstrated that, in addition to blocking the reuptake of catecholamines, cocaine binds to the putative sigma receptor in brain and peripheral tissues. We report here the identification of a sigma recognition site in the h uman placenta that has pharmacological characteristics similar to the neural sigma binding site. Placental tissues were obtained from pregna nt women that were matched on maternal demographic characteristics. Co caine exposure was confirmed by toxicology screens for cocaine and its metabolites in the urine and placental tissue. Sigma receptors were l abeled in placental membranes with +)[H-3]-3-3-hydroxy[phenyl]-N-(1-pr opyl)piperidine ([H-3]-(+)-3-PPP). Saturation analysis for [H-3]-(+)-3 -PPP revealed an apparent single class of binding sites with an affini ty constant comparable to the neural binding site (K(d) = 60-80 nM) an d mean B(max) values of 14 pmoles/g tissue. Competition assays demonst rated comparable rank order of potency and stereoselectivity for sigma ligands in human cerebellar and placental membranes. The density of s igma binding sites in placentas selected from cocaine using mothers we re significantly reduced as compared to control placentas matched for weight and gestational age. These findings suggest that the peripheral sigma binding site in the placenta is affected by cocaine exposure. T he cocaine-induced reduction in the number of placental sigma binding sites may reflect the direct and indirect effects of cocaine on the pl acenta and may further serve as an index of altered placental function .