The Influence of Prenatal Exposure to Methamphetamine on the Development of Dopaminergic Neurons in the Ventral Midbrain

Abstract

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.