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Interactive Effects of Tamoxifen and Oestrogen Upon the Nigrostriatal Dopaminergic System: Long-Term Treatments


Dean Dluzen Department of Anatomy, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44272-0095, USA


In the present report adult female rats were ovariectomized (OVX) and assigned to one of four treatment conditions. Treatments consisted of administering pellets containing 17β-oestradiol (E), tamoxifen (TMX), a combination of TMX and E or no further treatment (OVX). Animals received these treatments 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 stimulated DA output using in-vitro superfusion. No statistically significant differences among the four treatment groups were obtained for basal dopamine output. The highest levels of amphetamine-stimulated dopamine responses were obtained from E treated rats. These values were significantly greater than 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-traditional central nervous system site and mechanism of action through which tamoxifen–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 conditions where oestrogenic modulation is present.