Acute global anoxia during C-section birth affects dopamine-mediated behavioural responses and reactivity to stress

Abstract

Perinatal asphyxia may induce major neurological deficits shortly after birth as well as neurological/behavioural disorders later in development. We used a rat model of global perinatal asphyxia to model acute intrauterine asphyxia around the time of birth. Caesarean section was performed in rats and their pups, still in uterus horns, were placed into a water bath at 37 °C for periods of 0, 10 or 20 min. Pups were then given to surrogate mothers, and examined for long-term behavioural effects of the perinatal asphyctic insult. Behavioural assessment included analysis of novelty seeking behaviour at adolescence, while spatial discrimination abilities, response to both an acute and a chronic stress, and the effects of the full D1 receptor agonist SKF 82958 on open field behaviour were assessed at adulthood. Overall, no marked abnormalities were found in the novelty seeking test, in the ability to discriminate spatial changes in the test environment and in physiological response to stress. However, adult rats subjected to severe perinatal asphyxia (20 min) showed lower activity level and lower stereotyped behaviour after the administration of SKF 82958 in an open field test. These results support the observations from human and animal studies that perinatal insult can produce long-term dysfunction of dopaminergic neurotransmission, and points to the need of more thorough examination of the potential effects of perinatal asphyxia on hypothalamic–pituitary–adrenal (HPA) axis. Altogether, the present findings suggest that the present 20 min perinatal asphyxia model might serve for the study of neurodevelopmental disorders associated with perinatal insults.