Tamoxifen alters dopamine output through direct actions upon superfused corpus striatal tissue fragments
breast-cancer; receptor; Biochemistry & Molecular Biology; Neurosciences & Neurology; estrogen; breast-cancer; antagonist; estradiol; nigrostriatal; release; anti-estrogen; antiestrogens; metabolites; brain metastases; sexual-behavior; non-genomic
Tamoxifen (10 pg/ml) was infused directly into superfused striatal tissue fragments of ovariectomized rats for a 50 min period. Immediately following the termination of tamoxifen there was a significant increase in dopamine output compared with non-infused controls. No such significant increase was observed with use of a 100 pg/ml tamoxifen dose. Although dopamine output was again increased upon termination of a 2 h infusion of tamoxifen, these levels failed to differ significantly from that of non-infused controls. Similarly, a shorter 10 min duration infusion of tamoxifen failed to alter dopamine output. Finally, we examined whether the tamoxifen-induced, post-infusion increase in dopamine output, as observed following a 50 min infusion of 10 pg/ml, involved a calcium dependent process. To achieve this goal, superfusions were performed with Calcium/Tamoxifen, No Calcium/Tamoxifen, No Calcium/No Tamoxifen and Calcium/No Tamoxifen. A significant increase in dopamine output post-tamoxifen infusion was obtained for the Calcium/Tamoxifen condition compared with the remaining three groups which failed to differ from one another. Taken together these results show that tamoxifen can alter dopamine output through direct, non-genomic effects upon striatal neurons. Responses to this anti-estrogen are intriguing since they are apparent following removal, but not during tamoxifen infusion and represent a calcium-dependent process. These data suggest that tamoxifen may represent an important modulator of nigrostriatal dopaminergic function. (C) 1998 Elsevier Science Ltd. All rights reserved.
McDermott J L; Anderson L I; Dluzen D E
Neurochemistry International
1998
1998-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/s0197-0186(97)00086-7" target="_blank" rel="noreferrer noopener">10.1016/s0197-0186(97)00086-7</a>
TAMOXIFEN TREATMENT OF OVARIECTOMIZED MICE ALTERS DOPAMINE RELEASE FROM STRIATAL TISSUE FRAGMENTS SUPERFUSED IN-VITRO
rat; therapy; Neurosciences & Neurology; estrogen; metabolism; brain; breast-cancer; estradiol; nigrostriatal; pituitary; antiestrogens; uterus; anti-estrogen; caudate nucleus
In this report we examined the effect of tamoxifen upon the nigrostriatal dopaminergic system. Ovariectomized mice were subjected to one of the following treatments: two subcutaneous injections administered on successive days of the sesame oil vehicle (control), estradiol benzoate (EB-10 mu g), tamoxifen citrate (TMX 125 mu g) or a combination of EB + TMX. At 24 h after the second injection, the caudate nucleus was superfused in vitro to evaluate the effects of these treatments upon basal as well as potassium stimulated (30 mM) dopamine release rates. In addition, uteri were weighed from each animal. Basal and total fractional dopamine release rates from the caudate nucleus of control mice were significantly lower than those of the other three treatments, which failed to differ among each other. Potassium minus(-) basal stimulated dopamine release rates failed to differ significantly among the four treatment conditions. Uterine weights of the TMX treated mice were significantly greater than controls, but significantly lower than EB and EB + TMX animals. These data show that TMX can significantly increase caudate nucleus dopamine release to levels observed in EB treated mice. These agonistic effects of TMX upon nigrostriatal dopaminergic function can be contrasted with its relatively weak estrogenic effects upon uterine weights and indicate the discriminatory, system specific effects that can be exerted by this anti-estrogen. This demonstration of TMX's ability to modulate central nervous system function is of particular relevance in light of pending clinical trials for the prophylactic use of TMX in the treatment of women for breast cancer.
McDermott J L; Liu B J; Dluzen D E
Brain Research
1995
1995-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0006-8993(95)00993-z" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(95)00993-z</a>