The neurotoxic amphetamines include D-amphetamine (AMP), D-methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA), and p-chloroamphetamine. Since the late 1980s there has been a large increase in the use of METH44 and MDMA45, 46 including use among women of childbearing ages47-50 but there have been no long term studies of the neurodevelopmental consequences of prenatal MDMA in humans51. METH is a potent psychostimulant drug that has been shown to be neurotoxic to mature dopaminergic and serotonergic axons and axon terminal arbors52, and potentially neurotoxic to mature glutaminergic axons53. The cellular and molecular mechanisms implicated in the neurotoxicity induced by METH on mature neurons include the production of reactive oxygen species and nitric oxide, p53 activation resulting in apoptosis, and mitochondrial dysfunction54. Less is known about the mechanisms involved in METH-induced toxicity in the developing central nervous system. However, as mentioned above for cocaine, the early and widespread influence of serotonergic, dopaminergic and glutamatergic systems on neuronal growth and connectivity provides a strong theoretical basis for suspecting that prenatal exposure to METH and other neurotoxic amphetamines may also result in alterations in developing neural circuitry53.
