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Rats do not show cognitive impairment after breast cancer treatment with tamoxifen and methotrexate

Centen, M (2012) Rats do not show cognitive impairment after breast cancer treatment with tamoxifen and methotrexate. Master's Thesis / Essay, Biology.

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Abstract

Tamoxifen together with methotrexate is widely prescribed in estrogen receptor-α positive breast cancers, but reported complaints of impaired cognition after the use of these agents cause concern. Previous animal studies indicate a negative effect of methotrexate on cognition, but also negative effects of tamoxifen are reported. Tamoxifen is a so called selective estrogen modulator and acts via the estrogen receptor, either as an antagonist or agonist. Since estrogens are found to be important in cognition, the effect of tamoxifen via the estrogen receptors might explain the reported cognitive complaints. The aim of this study was to identify the effect of tamoxifen on anxiety and cognition either with or without methotrexate. The first study explored the effect of tamoxifen per se on anxiety and cognition in ovariectomized female wistar rats. The rats were treated with three weeks of tamoxifen (1 mg/kg) or vehicle daily. During the last week of treatment anxiety and cognitive behavior was measured in the open field; the elevated plus maze; the novel- and spatial object recognition test. Tamoxifen affected neither anxiety nor cognition in these behavior tests. In the second study the effect of tamoxifen was combined with methotrexate on anxiety and cognition in ovariectomized female Wildtype Groningen rats. The rats received an intraperitoneal (IP) injection with methotrexate (250 mg/kg) or vehicle, followed by three weeks of tamoxifen (2 mg/kg) or vehicle on a daily base. During the last week of treatment anxiety and cognitive behavior was measured in the open field and the elevated plus maze; the novel- and spatial object recognition test. Besides, spine- and synapse density in hippocampal tissue was measured through western blot analysis with antibodies against spinophilin and synaptophysin. Tamoxifen with or without methotrexate affected neither anxiety nor cognitive behavior; nor did it demonstrate changes in spine- or synapse density in hippocampal tissue. These studies indicate that tamoxifen with or without methotrexate does not affect anxiety or cognitive behavior in rats. Western blot analysis with antibodies against spinophilin and synaptophysin demonstrated no effect of tamoxifen with or without methotrexate on spine- or synapse density in the rat hippocampus. These findings suggest tamoxifen with or without methotrexate has no adverse or beneficial effects on cognition or anxiety.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Biology
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 07:58
Last Modified: 15 Feb 2018 07:58
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/12111

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