FUNCTIONAL AND MOLECULAR DIFFERENTIATION OF THE DOPAMINE SYSTEM INDUCED BY NEONATAL DENERVATION

The administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to dam age the mesostriatal dopamine (DA) system in the neonate results in di fferent neurochemical and behavioral consequences as compared to lesio ns made in adulthood. There have been few direct data to support the c onclusion that the behavioral changes following neonatal 6-OHDA lesion s reflect plasticity of the DA system. It is our hypothesis that the p lasticity of the developing DA system is fundamentally different from that of the adult. Responses to 6-OHDA lesions can only be understood within the context of the status of the mesostriatal DA system at the time of the lesion. There are stages of development in the early postn atal period when certain components of the mesostriatal DA system are differentially sensitive to 6-OHDA lesions. These ''windows'' of vulne rability can be predicted from an analysis of the developmental expres sion of DA receptors and the maturation of the subpopulation of the me sostriatal DA system that innervates them. We review the differences i n the behavioral plasticity of the adult and neonate sustaining 6-OHDA lesions to the mesostriatal DA system, the mechanisms responsible for the behavioral plasticity in the adult, and our conceptualization of which mechanisms are affected in the neonate. Copyright (C) Elsevier S cience Ltd.