Antiestrogen-induced alterations of hypothalamic dopamine and norepinephrine levels in the female rat

The influence of antiestrogen (tamoxifen) administration in vivo on the steady state concentration of dopamine (DA) and norepinephrine (NE) in the hypothalamus-median eminence area of mature female rats was investigated. Rats were treated with tamoxifen at 3 different dose levels (0.1, 1.0 and 10.0 mg/kg, s.c.) daily for 7 or 21 days. Control groups were injected with vehicle only (10% ethanol; 1.0 ml/kg). In a separate experiment, mature female rats were ovariectomized or sham operated and killed either 7 or 21 days after operation. Dopamine and NE were estimated by high pressure liquid chromatography with electro-chemical detection. Seven days of tamoxifen treatment at 3 different dose levels did not alter DA and NE concentrations compared to the control. The chronic (21 days) tamoxifen treatment in the smallest dose (0.1 mg) significantly increased the DA concentration. The concentration of NE was reduced only at the 1.0 mg/kg dose. There was no significant difference in the NE concentration 7 or 21 days after ovariectomy or sham operation, but the DA concentration was significantly increased 21 days after ovariectomy. The uterine weights were reduced significantly after 21 days of treatment with tamoxifen in the two larger doses, but were increased with the smallest dose of tamoxifen. Uterine weight after ovariectomy both after 7 and 21 days was significantly reduced. These results suggest that chronic low-dose antiestrogen treatment may affect the hypothalamic-median eminence DA and NE concentrations. The data also suggests that antiestrogenic action (uterine growth inhibition) of tamoxifen is not related to the alterations of DA and NE in the hypothalamus-median eminence.