Finally, a third major pathophysiologic pathway, fetal programming, has recently been proposed23 in which prenatal cocaine exposure may alter the expression of key candidate genes and gene networks important to placental function in late gestation. Two of the proposed candidate placental genes include norepinephrine transporter (NET) and 11-ß-dehydroxysteroid dehydrogenase type 2 (11ß-HSD-2), both of which modulate the fetal neuroendocrine environment by controlling catecholamine and glucocorticoid levels. Alterations in the expression of these genes and downstream effects on placental gene networks are hypothesized to cause developmental dysregulation in the HPA axis and subsequent long-term neurobehavioral effects.
