This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tamoxifen use for the prevention and treatment of breast cancer can have adverse emotional side-effects increasing the incidence of hot flashes and reducing feelings of emotional well being. Although treatment with anti-depressant medications, specifically serotonin reuptake inhibitors or SSRIs, could relieve these symptoms certain SSRIs may diminish the biological efficacy of tamoxifen by altering enzymes that change the metabolism of tamoxifen into its less active forms. We have been using adult female rhesus monkeys to study how two SSRIs, paroxetine and citalopram, differentially affect the metabolism of tamoxifen and how these medications affect the anxiety producing effects of tamoxifen. The analyses of the data thus far indicate that paroxetine but not citalopram changes the metabolism of tamoxifen to its less biologically active forms. Importantly, indices of anxiety were CO-INV: attenuated during treatment with either anti-anxiety medications. Although these data are preliminary, they suggest that citalopram may have beneficial effects on behavior without affecting tamoxifen' s cancer fighting activity.
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