Interactive effects of tamoxifen and oestrogen upon the nigrostriatal dopaminergic system: Long-term treatments

In the present report adult female rats were ovariectomized (OVX) and assig ned to one of four treatment conditions. Treatments consisted of administer ing pellets containing 17 beta-oestradiol (E), tamoxifen (TMX), a combinati on of TMX and E or no further treatment (OVX), Animals received these treat ments immediately following OVX and were maintained in these conditions for a 40-day period. Subsequently, the corpus striatum (CS) was dissected from each animal and prepared for determinations of basal and amphetamine stimu lated DA output using in-vitro superfusion. No statistically significant di fferences among the four treatment groups were obtained for basal dopamine output. The highest levels of amphetamine-stimulated dopamine responses wer e obtained from E treated rats. These values were significantly greater tha n that obtained from OVX rats and rats treated with a combination of TMX E. The significance of these findings is that they indicate both a non-trad itional central nervous system site and mechanism of action through which t amoxifen-oestrogen interactions can function. Such data may have important implications for administration of tamoxifen to premenopausal women as this anti-oestrogen may compromise nigrostriatal dopaminergic function under co nditions where oestrogenic modulation is present.