Effects of prenatal diazepam treatment on Mycobacterium bovis-induced infection in hamsters

In utero exposure of rats to low dosages of diazepam has been found to result in depression of cellular and humoral immune responses during adulthood, with marked changes in macrophage spreading and phagocytosis. The present experiment was undertaken to investigate the resistance of adult hamsters to Mycobacterium bovis after prenatal exposure to diazepam. Time-pregnant hamsters were exposed to diazepam (1.0 or 1.5 mg kg(-1) day(-1) subcutaneously) or vehicle from gestational day 9 to 15. A total of 36 different litters (12 of them control and 12 for each experimental group) born after a 16/17-day gestation were used. One male from each litter was infected twice with identical inoculum concentrations of M. bovis at 75 and 107 days of age. This infection model involves the participation of macrophages and T and B cell populations. The animals prenatally exposed to the higher (1.5 mg/kg) dose of diazepam exhibited: (1) increased weight loss, (2) increased mortality, (3) increased granuloma areas measured in the liver, lung and spleen, (4) increased spleen weight, and (5) increased scores of M. bovis colony forming units (CFU) isolated from liver, lung and spleen. These effects were dose-dependent, and were not detected or were less severe in animals treated with the lower (1.0 mg/kg) dose of diazepam as well as in those of the control group. The present data demonstrate an impaired defence against M. bovis in adult hamsters after in utero exposure to a dosage of 1.5 mg/kg of diazepam.