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 assigned to one of four treatment conditions. Treatments consisted of administering pellets containing 17beta-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.
McDermott
J L
JL
Department of Medicine, Edwin Shaw, Hospital, Akron, OH, USA.
Anderson
L I
LI
Dluzen
D E
DE
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D004298:Dopamine / Q000096:biosynthesis; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*; D013995:Time; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D013629:Tamoxifen; D004958:Estradiol; D000661:Amphetamine; D004298:Dopamine