In a study designed to examine the role of the genotype on sensitivity to drug-induced behavioural changes, pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital (PHB) intraperitoneally during days 10-16 of gestation. Following a balanced intrastrain fostering procedure, the behaviour of lactating dams was observed in their home cage at 2, 3, 5, 7 and 14 days postpartum. As the pups became older, maternal behaviour declined in control groups, whereas PHB dams of the CBA strain persisted in nursing their pups. C57 dams were generally affected in an opposite way by PHB exposure. For example, treated dams spent significantly less time in licking behaviour. Nest quality score was especially elevated in PHB dams of the CBA strain, while in C57 dams, nest-building was inhibited and nest quality unaffected by the previous PHB exposure. These results indicate that specific items of maternal behaviour can be differently affected by PHB exposure, and that the responses are affected by the genotype. To summarise, pups raised by treated dams may receive either exaggerated or insufficient maternal attention, as a result of changes in neurotransmitter systems and behavioural regulation following phenobarbital exposure. These results point to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on postnatal development.
Pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital intraperitoneally from days 10 to 16 of gestation. On day 18 of pregnancy half of the control and drug-treated mice were killed and the embryonic brains removed for cell cultures. The remaining mice were allowed to have their litter. After cross-fostering the mice were used for behavioural studies. Pups born to drug-treated CBA mice had birth-weights similar to controls, but their weights had fallen behind controls by day 18 after birth. They were slower at attaining mature responses in tests for sensory motor development and became progressively more hyperactive (three times more active at day 18) compared to controls. Drug-exposed C57 pups also had birth weights similar to controls. After cross-fostering, 19% of control and 31% of drug-exposed pups died, but the remaining drug-exposed pups showed no deficits in weight gain. In contrast to drug-treated CBA pups, drug-exposed C57 pups were slightly quicker in attaining mature responses in some tests. There was no difference in activity between them and their controls. In neurochemical analyses, uptake of neurotransmitters by cerebral cultures from CBA showed that uptake of GABA was increased by 5%, choline by 95%, dopamine 120%, serotonin 165% and noradrenaline by 160% in cultures from drug exposed embryos compared to controls. In cerebral cultures from C57, GABA uptake was reduced by 18%, choline 33%, dopamine 35% and noradrenaline by 25%. Only serotonin uptake was increased by 182% compared to controls. Differences between C57 and CBA were also apparent in the uptake of neurotransmitters by neuronal cultures from the mesencephalon.(ABSTRACT TRUNCATED AT 250 WORDS)
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