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 af fect immune functions (25,26). Because the immune system is controlled by the autonomic nervous system, we investigated the sympathetic acti vity in the spleen for a possible contribution to impaired immune func tion. Twenty-eight-day-old offspring of prenatally diazepam- or vehicl e-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 hig her in females than in males. Prenatal diazepam treatment resulted in reduced NA turnover in the spleen of SRBC-stimulated female, but not m ale. offspring. Beta-Adrenergic binding sites in spleen membrane fract ions, studied with H-3-dihydroalprenolol, showed no differences, indic ating that changes in NA turnover were not compensated by changes in r eceptor expression. Sex-specific developmental effects of diazepam hav e been described earlier, e.g., in selective effects on perinatal cort icosterone levels in female offspring (26).