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

• Published in: The Journal of neuroscience Vol. 20; no. 14; pp. 5538 - 5543
• Main Authors: Brake, Wayne G, Sullivan, Ron M, Gratton, Alain
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 15.07.2000; Society for Neuroscience
• Subjects: Analysis of Variance; Animals; Carrier Proteins - metabolism; Cesarean Section; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins; Female; Fetal Hypoxia - physiopathology; Functional Laterality; Male; Membrane Glycoproteins; Membrane Transport Proteins; Motor Activity; Nerve Tissue Proteins; Prefrontal Cortex - physiopathology; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Receptors, Dopamine - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.20-14-05538.2000

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 D(1) and D(2) 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.