Tamoxifen alters dopamine output through direct actions upon superfused corpus striatal tissue fragments.
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.
McDermott
J L
JL
Department of Medicine, Edwin Shaw Hospital, Akron, Ohio 44312-4495, USA.
Anderson
L I
LI
Dluzen
D E
DE
D000818:Animals; D002118:Calcium / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D046508:Culture Techniques; D015194:Diffusion Chambers, Culture; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D010052:Ovariectomy; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
D013629:Tamoxifen; D002118:Calcium; D004298:Dopamine