TAMOXIFEN ALTERS DOPAMINE OUTPUT THROUGH DIRECT ACTIONS UPON SUPERFUSED CORPUS STRIATAL TISSUE FRAGMENTS

Tamoxifen (10 pg/ml) was infused directly into superfused striatal tis sue fragments of ovariectomized rats for a 50 min period. Immediately following the termination of tamoxifen there was a significant increas e in dopamine output compared with non-infused controls. No such signi ficant increase was observed with use of a 100 pg/ml tamoxifen dose. A lthough dopamine output was again increased upon termination of a 2 h infusion of tamoxifen, these levels failed to differ significantly fro m that of non-infused controls. Similarly, a shorter 10 min duration i nfusion of tamoxifen failed to alter dopamine output. Finally, we exam ined 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 di ffer from one another. Taken together these results show that tamoxife n can alter dopamine output through direct, non-genomic effects upon s triatal 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 ta moxifen may represent an important modulator of nigrostriatal dopamine rgic function. (C) 1998 Elsevier Science Ltd. All rights reserved.