Drugs of abuse and human placenta

Abstract

Drugs of abuse such as cocaine and amphetamines, when used by pregnant women, exert deleterious effects on the fetus. These drugs produce their effects through inhibition of the serotonin transporter, norepinephrine transporter, and dopamine transporter. The inhibition can occur in the pregnant mother as well as in the fetus. These events contribute to the detrimental effects of these drugs on the fetus. However, the role of placenta, which serves as the link between the pregnant mother and the fetus, in the process remains understudied. It has been assumed that the placenta did not play any direct role in the process except that it allowed the passage of these drugs from maternal circulation into fetal circulation. This was before the discovery that the placenta expresses two of the three monoamine transporters. The serotonin transporter and the norepinephrine transporter are expressed on the maternal-facing side of the syncytiotrophoblast, thus exposed to the inhibitory actions of cocaine and amphetamines if present in maternal blood. Inhibition of these transporters in the placenta could lead to elevation of serotonin and norepinephrine in the intervillous space that may cause uterine contraction and vasoconstriction, resulting in premature delivery, decreased placental blood flow, and intrauterine growth retardation. Thus, the placenta is actually a direct target for these abusable drugs. Since the placental serotonin transporter and norepinephrine transporter are also inhibited by many antidepressants, therapeutic use of these drugs in pregnant women may have similar detrimental effects on placental function and fetal growth and development.

Fig. 1

Physiologic functions of the serotonin transporter (■) and norepinephrine transporter (●) in human placental trophoblast. 5HT, serotonin (also called 5-hydroxytryptamine); NE, norepinephrine; E, epinephrine. These two transporters are located on the maternal-facing brush border membrane of the trophoblast.

Fig. 2

Roles of the serotonin transporter and norepinephrine transporter in the nervous system. A, serotonin transporter; B, norepinephrine transporter; V, vesicular monoamine transporter; 5HT, serotonin; NE, norepinephrine; Trp, tryptophan; MAO, monoamine oxidase; Phe, phenylalanine; Tyr, tyrosine; DA, dopamine.

Fig. 3

Differential actions of cocaine and amphetamines on placental serotonin and norepinephrine transporters. 5HT, serotonin; NE, norepinephrine; ■, serotonin transporter; ●, norepinephrine transporter.