Mook Deborah, Felger Jennifer, Graves Franklynn, Wallen Kim, Wilson Mark E
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
Psychoneuroendocrinology. 2005 Apr;30(3):273-83. doi: 10.1016/j.psyneuen.2004.08.005.
The selective estrogen receptor modulator (SERM), tamoxifen, effectively slows the progression of estrogen-positive breast cancer and aids in the prevention of cancer in at-risk women. Tamoxifen is well characterized with regards to its effects on breast cancer, but its effects on other estrogen-related systems, particularly neural circuits regulating brain function and mood, are poorly understood. Using ovariectomized rhesus monkeys, we examined the effects of tamoxifen, with and without estrogen replacement therapy (ERT), on social behavior and central serotonin (5HT) systems thought to influence these behaviors. Relative to placebo treatments, estrogen treatment increased serotonergic tone, based on response in prolactin and cortisol to fenfluramine, a 5HT releasing agent. Tamoxifen neither blocked nor enhanced this effect, indicating it to be neither an antagonist nor an agonist on serotonergic activity. In contrast, CSF measures of the 5HT metabolite, 5HIAA, were not significantly affected by treatment. Tamoxifen-treated animals showed increases in measures of anxiety, compared with ERT-treated animals, suggesting that this SERM may be anxiogenic. Co-treatment with estrogen attenuated the anxiogenic properties of tamoxifen. These data show that tamoxifen administration increased anxiety levels, but the affect was not associated with differences in central levels of the serotonin tone.
选择性雌激素受体调节剂（SERM）他莫昔芬可有效减缓雌激素阳性乳腺癌的进展，并有助于预防高危女性患癌。他莫昔芬对乳腺癌的作用已得到充分研究，但其对其他雌激素相关系统的影响，尤其是对调节脑功能和情绪的神经回路的影响，却知之甚少。我们利用去卵巢恒河猴，研究了他莫昔芬在有或无雌激素替代疗法（ERT）情况下，对社交行为以及被认为会影响这些行为的中枢5-羟色胺（5HT）系统的作用。相对于安慰剂治疗，基于催乳素和皮质醇对5HT释放剂芬氟拉明的反应，雌激素治疗可提高血清素能张力。他莫昔芬既不阻断也不增强这种作用，表明它对血清素能活性既不是拮抗剂也不是激动剂。相比之下，脑脊液中5HT代谢物5-羟吲哚乙酸（5HIAA）的测量值不受治疗的显著影响。与ERT治疗的动物相比，他莫昔芬治疗的动物焦虑测量值增加，表明这种SERM可能具有致焦虑作用。雌激素联合治疗可减弱他莫昔芬的致焦虑特性。这些数据表明，给予他莫昔芬会增加焦虑水平，但这种影响与中枢血清素能张力水平的差异无关。
