Sex-dependent effects of tamoxifen on mouse behavior
Abstract
This study aimed to investigate the sex-dependent behavioral effects of tamoxifen, commonly used to induce Cre recombination in transgenic systems, across three developmental stages (adult, adolescent, and neonatal) and two CreERT2 mouse lines (CaMKIIα-CreERT2 and Aldh1l1-CreERT2). Both male and female mice, including wild-type C57BL/6J and CreERT2 transgenic lines, were subjected to tamoxifen treatment followed by behavioral tests assessing locomotion, anxiety-like behavior (open field test and elevated plus maze), social interaction, recognition memory (new object recognition), sucrose preference, and depression-like behavior (forced swimming test) at least 4 weeks post-treatment. We found that adult tamoxifen treatment increased depression-like behavior specifically in males, while adolescent treatment increased sucrose preference only in males, yet impaired recognition memory and increased depression-like behavior in both sexes. Neonatal treatment caused pervasive impairments, reducing locomotion and increasing anxiety- and depression-like behavior in both sexes, while enhancing social interaction only in males. Furthermore, effects differed in adult CaMKIIα-CreERT2 and Aldh1l1-CreERT2 mice. In the former, tamoxifen treatment impaired locomotion, increased anxiety-like behavior, and reduced recognition memory specifically in females, while increasing sucrose preference in males. In the latter, tamoxifen treatment impaired recognition memory in both sexes but increased…
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