Phenobarbitone: adverse effects on reproductive performance and offspring development in the Mongolian gerbil, (Meriones unguiculatus)

Abstract

Phenobarbitone at a concentration of 500 mg/l in drinking fluid of gerbils during pregnancy (60 mg/kg) and lactation (136 mg/kg) markedly reduced the proportion of animals bearing litters, decreased pup weights at birth and during later life and delayed development of the self-righting reflex, auditory startle reaction, eye opening and full fur coverage. It also prolonged the period of suckling. Scars of implantation were evident in uterine horns of 60% of treated and in none of control females that had failed to give birth. Treated offspring after weaning were given phenobarbitone (500 mg/l; 42-124 mg/kg) as their drinking fluid throughout life and a further group of gerbils received this concentration of the drug from the time of weaning. Seizure susceptibility was unaltered by the drug treatment, and the only evidence of behavioural change was seen in offspring gerbils at 6 weeks when the bout length of social investigation during encounters was increased. Drug-treated offspring showed no abnormality in brain weight relative to body weight. Weight gain and brain weight remained normal among the gerbils given phenobarbitone after weaning. The drug treatment reduced scent gland size in breeding males, though not in the offspring, and had no effect on weights of the testes or ovaries and uterus. no effect on weights of the testes or ovaries and uterus. Plasma concentrations of phenobarbitone in females of the postweaning group amounted on average to 4.4 mg/kg. Most of the adverse effects of this dose of phenobarbitone in the gerbil can thus be seen to be associated either with reproductive impairment or with exposure during sensitive periods of early development.