Perinatal distress leads to lateralized medial prefrontal cortical dopamine hypofunction in adult rats

Obstetric complications involving anoxia or prolonged hypoxia are suspected to increase the risk for such mental disorders as schizophrenia and attent ion deficit-hyperactivity disorder. In previous studies, we reported eviden ce of enhanced nucleus accumbens (NAcc) dopamine (DA) function in adult rat s subjected to intrauterine anoxia during cesarean (C) section birth. In th e present study, we used voltammetry and monoamine-sensitive electrodes to investigate the possibility that this functional hyperactivity of the meso- NAcc system is attributable to a loss of inhibitory control from the medial prefrontal cortex (PFC). We monitored the DA responses to repeated once-da ily stress in the right or left PFC of adult male rats born vaginally (VAG) or by C-section, either with (C + 15) or without (C + 0) an additional 15 min of intrauterine anoxia. In C + 15 animals, we observed a pronounced and persistent blunting of stress-induced DA release in the right PFC but not in the left; with repeated testing, a similar pattern of dampened right PFC DA stress responses emerged in C + 0 animals. In addition, C + 15 animals were spontaneously more active than VAG and C + 0 animals and displayed an increase in PFC DA transporter density that was also lateralized to the rig ht hemisphere. There was no evidence, however, that PFC D-1 and D-2 recepto r levels differed between birth groups or hemisphere. These findings sugges t a mechanism by which perinatal complications involving anoxia might contr ibute to the etiology of mental disorders that have been linked to disturba nces in central DA transmission and lateralized PFC dysfunction.