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Perinatal distress leads to lateralized medial prefrontal cortical dopamine hypofunction in adult rats
W G Brake1, R M Sullivan, A Gratton
1Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021, USA.
Insights
Obstetric anoxia may impact brain development, potentially increasing mental disorder risk. This study found that perinatal anoxia can alter dopamine responses in the medial prefrontal cortex, suggesting a mechanism for these disorders.
Area of Science:
- Neuroscience
- Developmental Psychology
- Psychiatry
Background:
- Obstetric complications like anoxia are linked to increased risk of mental disorders.
- Previous research indicated enhanced nucleus accumbens dopamine function in rats with intrauterine anoxia during C-section birth.
Purpose of the Study:
- To investigate if hyperactivity in the meso-nucleus accumbens dopamine system is due to reduced inhibitory control from the medial prefrontal cortex.
- To examine the effects of perinatal anoxia on dopamine responses to stress in the medial prefrontal cortex.
Main Methods:
- Used voltammetry and monoamine-sensitive electrodes to monitor dopamine responses.
- Studied adult male rats born vaginally or via C-section, with or without intrauterine anoxia.
- Administered repeated daily stress to assess dopamine release in the medial prefrontal cortex.
Main Results:
- Animals experiencing intrauterine anoxia showed blunted stress-induced dopamine release in the right medial prefrontal cortex.
- A similar dampened dopamine response in the right medial prefrontal cortex was observed in C-section born rats without anoxia after repeated stress.
- Anoxia-exposed rats exhibited increased spontaneous activity and lateralized dopamine transporter density in the right prefrontal cortex.
Conclusions:
- Perinatal anoxia may lead to lateralized dysfunction in the medial prefrontal cortex dopamine system.
- This dysfunction could be a mechanism contributing to the etiology of mental disorders associated with central dopamine transmission disturbances.
Abstract:
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.
