Long-term effects of perinatal asphyxia on basal ganglia neurotransmitter systems studied with microdialysis in rat

Abstract

Asphyxia was induced in pups delivered by caesarean section on pregnant Sprague-Dawley rats. Rats within the last day of gestation were anaesthetised and hysterectomized. The uterus horns including the foetuses were placed in a water bath for various periods of time. Following asphyxia the uterus horns were opened. The pups were removed, stimulated to breathe, left to recover and given to surrogate mothers. Control and asphyctic pups were obtained from each mother. Rats surviving asphyctic periods longer than 20 min at 37°C showed chronic deficits in the release of neurotransmitters monitored with microdialysis in the basal ganglia. The main change observed in 6-month-old male rats that underwent severe perinatal asphyxia was a marked decrease in striatal dopamine release, monitored under basal and d-amphetamine stimulated conditions, as compared with control (normal- or caesarean-delivered) rats. Striatal glutamate and aspartate levels were also decreased following asphyxia. In the substantia nigra, the main effect of asphyxia was a decrease of both γ-aminobutyric acid (GABA) and aspartate levels. Thus, this study provides evidence that perinatal asphyxia leads to chronic deficits in neurotransmission in the basal ganglia.