Prenatal exposure to drugs of abuse in humans: effects on placental neurotransmitter receptors.

Recently, the concept of behavioral teratology has evolved. In animal models, prenatal exposure to low doses of psychotropics (e.g., methadone, diazepam) results in abnormal development of behavior. Furthermore, in animals, pre- and perinatal exposure to psychoactive drugs results in altered brain neurochemistry. In humans, similar behavioral and neurological disruptions have been reported. The mechanisms responsible for these effects are unknown; however, all of these psychotropics have high affinity, specific interactions with various neurotransmitter receptors. Furthermore, normal development of nervous tissue appears to be mediated through neurotransmitter receptors. Disruption of normal, receptor-mediated "signals" by psychoactive agents would be expected to alter development of brain. In order to examine the regulation of neurotransmitter receptors by centrally acting agents, we have compared placental neurotransmitter receptors from "control" and substance-abusing women, hypothesizing that (1) placental neurotransmitter receptor regulation may mirror fetal brain neurotransmitter receptor regulation and (2) placental neurotransmitter receptors themselves may play a role in development. Standard radioligand binding methods were employed. Control values were relatively consistent while substance-abusing values were inconsistent, with wide variation in each substance-abusing group, possibly indicative of "regulation" of neurotransmitter receptors, yet certainly complicated by other variables surrounding gestation and birth (e.g., drug dosage and schedule, length of labor). In this regard, levels of neurotransmitter receptors were consistently higher (20-100%) in caesarian section tissue, possibly reflecting "down-regulation" of neurotransmitter receptors in placentas by the known excess sympathetic and opiate activity during labor.(ABSTRACT TRUNCATED AT 250 WORDS)