Interactive effects of tamoxifen and estrogen upon the nigrostriatal dopaminergic system

Interactive effects of tamoxifen and estrogen upon the nigrostriatal dopaminergic system

McDermott J L; Anderson L I; Dluzen D E

Neuroendocrinology

1997

1997-09

Adult female rats were ovariectomized and received a 21-day release pellet containing either (17)beta-estradiol (0.1 mg), tamoxifen (5.0 mg), a combination of estradiol and tamoxifen or no further treatment. At 14 days following ovariectomy +/- hormone treatments rats were sacrificed, the corpus striatum removed and prepared for assessment of dopamine release using in vitro superfusion. Maximal potassium-stimulated dopamine release rates were obtained with the estradiol + tamoxifen-treated rats and these levels were significantly greater than those from animals receiving only tamoxifen. Similarly, maximally amphetamine-stimulated responses were obtained from estradiol + tamoxifen-treated rats, however, in contrast to potassium, these values were significantly greater than both animals receiving either estradiol or tamoxifen alone. These data demonstrate that the nigrostriatal dopaminergic system appears particularly sensitive to the modulatory effects of a combined treatment with estradiol + tamoxifen. Moreover, some of the potential mechanisms of these responses are indicated by the differential dopamine outputs as evoked by potassium or amphetamine. The significance of these synergistic actions is their potential to mimic changes that may occur under conditions of tamoxifen treatment of premenopausal women as has been suggested for women at risk for breast cancer.

breast-cancer; rat; receptors; Neurosciences & Neurology; Endocrinology & Metabolism; catecholamines; breast-cancer; striatum; uptake sites; amphetamine; Progesterone; female cd-1 mice; release; antiestrogens; brain metastases; chronic estradiol; ovarian steroids; sexual-behavior

Journal Article or Conference Abstract Publication

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