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The Journal of Neuroscience, July 15, 2000, 20(14):5538-5543

Perinatal Distress Leads to Lateralized Medial Prefrontal Cortical Dopamine Hypofunction in Adult Rats

Wayne G. Brake¹, Ron M. Sullivan², and Alain Gratton²

¹ Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021, and ² Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montréal, Canada H4H 1R3

Obstetric complications involving anoxia or prolonged hypoxia are suspected to increase the risk for such mental disorders as schizophrenia and attention deficit-hyperactivity disorder. In previous studies, we reported evidence of enhanced nucleus accumbens (NAcc) dopamine (DA) function in adult rats subjected to intrauterine anoxia during cesarean (C) section birth. In the 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-daily 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 right hemisphere. There was no evidence, however, that PFC D₁ and D₂ receptor levels differed between birth groups or hemisphere. These findings suggest a mechanism by which perinatal complications involving anoxia might contribute to the etiology of mental disorders that have been linked to disturbances in central DA transmission and lateralized PFC dysfunction.

Key words: stress; voltammetry; cesarean section; anoxia; obstetric complications; dopamine transporter; asymmetry; attention deficit/hyperactivity disorder

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20145538-06$05.00/0

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