4.4 Article

Epinephrine administration at birth prevents long-term changes in dopaminergic parameters caused by Cesarean section birth in the rat

Journal

PSYCHOPHARMACOLOGY
Volume 200, Issue 3, Pages 381-391

Publisher

SPRINGER
DOI: 10.1007/s00213-008-1213-9

Keywords

amphetamine; Cesarean section; dopamine transporter; epinephrine; locomotion; obstetric complications; perinatal hypoxia; schizophrenia; tyrosine hydroxylase

Funding

  1. Canadian Institutes of Health Research

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Rationale Obstetric complications involving birth hypoxia are implicated in the etiology of disorders with dopaminergic dysfunction, such as schizophrenia. Cesarean section (C-section) birth in both humans and rats is associated with increased mild respiratory distress and with reduced levels of circulating catecholamines at birth, which normally serve to prime the lungs and activate other processes promoting extrauterine adaptation. Using a rat model, it has been found that C-section birth can produce long-term changes in central nervous system (CNS) dopamine function, compared to vaginal birth. Objective The present experiments tested if administering exogenous epinephrine at birth could reverse long-term changes in dopaminergic parameters in C-sectioned rats. Results In the absence of stress at adulthood, no differences were observed between C-sectioned and vaginally born rats in levels of in vivo tyrosine hydroxylase (TH) activity and dopamine transporter (DAT) binding. However, after repeated mild stress at adulthood, C-sectioned rats showed increased TH activity in nucleus accumbens and increased DAT in dorsal striatum and accumbens, compared to vaginally born controls. A single injection of epinephrine to C-sectioned rats just after birth prevented the increased TH activity and DAT binding seen in C-sectioned rats after repeated mild stress at adulthood. There was also a trend for epinephrine at birth to partially reverse an increase in amphetamine-induced locomotion seen in C-sectioned rats at adulthood. Conclusions These results suggest that variations in levels of circulating catecholamines in the neonate at the time of birth could contribute to subtle long-term changes in CNS function.

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