Birth insult increases amphetamine-induced behavioral responses in the adult rat

We have previously reported that an apparently uncomplicated Caesarean section birth produces long-term alterations in steady-state levels of dopamine in the central nervous system of the rat. In addition, adult rats that had been born by Caesarean section, either with or without acute global anoxia, showed markedly greater dopamine release from the nucleus accumbens in response to repeated stress, in comparison to vaginally born controls. The aim of the present study was to test whether these birth complications also result in long-term changes in behavior mediated by dopamine systems. For this, we investigated effects of a low dose (0.5 mg/kg) of amphetamine on activity levels in three-month-old rats that had been born vaginally (control), by rapid Caesarean section, or by Caesarean section with 15 min of global anoxia. Amphetamine induced a significantly greater increase in locomotor activity in animals born by Caesarean section or by Caesarean section+ 15 min anoxia, in comparison to the drug's effects in vaginally born controls. Behavioral responses were further analysed from video recordings of the animals' behavior. In confirmation of automated activity counts, both animals born by Caesarean section and by Caesarean section + 15 min anoxia showed a significant increase in the duration and frequency of moving and a decrease in the duration and frequency of standing, in comparison to vaginally born controls. Animals delivered by Caesarean section showed a significant increase in the duration of sniffing and a decrease in the duration and frequency of grooming when compared to vaginally born controls. Animals delivered by Caesarean section + 15 min anoxia showed a significant increase in the duration and frequency of rearing, in comparison to controls. The pattern of behavioral changes observed indicates that, as adults, animals born by Caesarean section and by Caesarean section with added global anoxia both show heightened behavioral responses to amphetamine, in comparison to vaginally born animals. These findings highlight the sensitivity of dopamine pathways to variations in birth procedure and add experimental support to epidemiological evidence implicating birth complications in the pathophysiology of disorders involving central dopaminergic neurons, such as schizophrenia.