Opiate withdrawal during development: are NMDA receptors indispensable?

Despite decades of research, the mechanisms that underlie opiate tolerance, dependence and withdrawal remain elusive. Evidence accumulated over the pa st ten years suggests that the NMDA receptor plays a central role in mediat ing the neuroplasticity induced by chronic opiate administration in adult a nimals. Yet, during ontogeny, the NMDA receptor complex undergoes qualitati ve developmental changes, which renders some of the basic assumptions for a role of the NMDA receptor in opiate withdrawal invalid in infants. Recent data indicate that NMDA receptor antagonists are not effective in blocking morphine tolerance, dependence and withdrawal in the neonatal rat. Roles fo r other glutamate receptor types (e.g. metabotropic glutamate receptors) ha ve also been proposed recently. In this article, the latest evidence that c haracterizes the dynamic roles of glutamate receptors in these phenomena du ring ontogeny will be discussed.