Neurodevelopmental consequences of early exposure to phencyclidine and related drugs

In the early development of the central nervous system, stimulation of N-me thyl-D-aspartate (NMDA) receptors may be critical for neuronal cell surviva l and differentiation, as well as the establishment of neural networks resu lting from ''experience-dependent plasticity." The trophic influence of NMD A receptor stimulation may be present only during a certain critical period of development. There are, therefore, major concerns associated with the a dministration of noncompetitive NMDA receptor antagonists (such as MK-801 [ dizocilpine]) as neuroprotective and anticonvulsant agents to pregnant wome n, neonates, infants, and young children. Several studies showing disruptiv e effects of noncompetitive NMDA receptor antagonists on normal neurobehavi oral development are reviewed in this article. This research has important public health implications because phencyclidine (PCP), a noncompetitive NM DA receptor antagonist, is a frequently-abused drug that may disrupt brain development in utero when abused by pregnant women. The article also review s studies of neonatal blockade of the NMDA receptor complex in animals; stu dies that may lead to useful models of human neurodevelopmental disorders. These models may even mimic the relevant neurodevelopmental aspects of at l east some forms of schizophrenia, especially the early developmental discon nection of circuits between the hippocampus and frontal cortex.