Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders

Abstract

Altered subcortical dopaminergic activity is thought to be involved in the pathophysiology of several disorders including schizophrenia, substance abuse and attention deficit hyperactivity disorder. Epidemiological studies have implicated perinatal insults, particularly obstetric complications involving fetal or neonatal hypoxia, as etiological risk factors for schizophrenia. This suggests the possibility that perinatal hypoxia might have lasting effects on dopaminergic function. In animal models, dopaminergic systems appears to be particularly vulnerable to a wide range of perinatal insults, resulting in persistent alterations in function of mesolimbic and mesostriatal pathways. This review summarizes recent work characterizing long-term changes in dopaminergic function and biochemistry in models of Caesarean section (C-section) birth and of C-section birth with added global anoxia in the rat and guinea pig. C-section birth and C-section with anoxia appear to be two distinct hypoxic birth insults, with somewhat differing patterns of lasting effects on dopamine systems. In addition, birth insult alters the manner in which dopaminergic function is regulated by stress at adulthood. The possible relevance of these finding to effects of human birth procedures is discussed.