Prenatal exposure to diazepam causes sex-dependent changes of the sympathetic control of rat spleen.

Prenatal exposure to low doses of benzodiazepines has been found to affect immune functions (25,26). Because the immune system is controlled by the autonomic nervous system, we investigated the sympathetic activity in the spleen for a possible contribution to impaired immune function. Twenty-eight-day-old offspring of prenatally diazepam- or vehicle-treated Long-Evans rats (diazepam 1.25 mg/kg/day SC, gestational day 14-20) were injected IP with sheep red blood cells (SRBC) to evoke an immune reaction. Baseline splenic noradrenaline (NA) turnover was higher in females than in males. Prenatal diazepam treatment resulted in reduced NA turnover in the spleen of SRBC-stimulated female, but not male, offspring. beta-Adrenergic binding sites in spleen membrane fractions, studied with 3H-dihydroalprenolol, showed no differences, indicating that changes in NA turnover were not compensated by changes in receptor expression. Sex-specific developmental effects of diazepam have been described earlier, e.g., in selective effects on perinatal corticosterone levels in female offspring (26).