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The California mouse (<jats:italic>Peromyscus californicus<\/jats:italic>) is a rare monogamous mouse species that offers a novel opportunity to model human intimate partnership to identify the neurobiological mechanisms by which mate bonding reduces chemotherapy-associated behavioral side effects. As a first step toward this goal, this pilot study aimed to develop the first chemotherapy model, to our knowledge, in adult male and female California mice. Following a repeated paclitaxel chemotherapy regimen, well characterized in laboratory mice (<jats:italic>Mus musculus<\/jats:italic>), gross sickness physiology was first assessed after various doses. The 20\u2005mg\/kg paclitaxel dose, injected six times every other day, was the highest tolerable, clinically relevant dose and was characterized by moderate body mass loss and increased spleen mass. Thus, further investigation of the effects of this chemotherapy paradigm on peripheral and neural inflammatory gene expression, based on previous reports in laboratory mice, was undertaken; results were mixed. Consistent across the spleen, hippocampus, and hypothalamus, some proinflammatory genes were unexpectedly decreased with chemotherapy (<jats:italic>Il1\u03b2<\/jats:italic>, <jats:italic>Tnf<\/jats:italic>), whereas one gene was increased (<jats:italic>Icam1<\/jats:italic>). Chemotherapy also increased fatigue and sociability, but not anxiety-like behavior or cognition. Taken together, this pilot study characterized a translational model of chemotherapy in California mice with clinically relevant gross physiological changes and modest changes in neuroinflammation and behavioral side effects. This work also highlights the need for comparative studies and the growth of research tools for this socially relevant mouse species.<\/jats:p>","DOI":"10.1523\/eneuro.0159-25.2025","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T17:50:14Z","timestamp":1757008214000},"page":"ENEURO.0159-25.2025","update-policy":"https:\/\/doi.org\/10.1523\/eneuro.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of a Monogamous California Mouse Model of Chemotherapy"],"prefix":"10.1523","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8284-8297","authenticated-orcid":false,"given":"Melina M.","family":"Seng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4961-2836","authenticated-orcid":false,"given":"Zoe M.","family":"Tapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1938-2144","authenticated-orcid":false,"given":"Erica R.","family":"Glasper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-0663","authenticated-orcid":false,"given":"Leah M.","family":"Pyter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"2025092210500553000_12.9.ENEURO.0159-25.2025.1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3390\/ijms21010022","article-title":"How to make anticancer drugs cross the blood-brain barrier to treat brain metastases","volume":"21","author":"Angeli","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2025092210500553000_12.9.ENEURO.0159-25.2025.2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2015.0122"},{"key":"2025092210500553000_12.9.ENEURO.0159-25.2025.3","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200108)31:8<2448::AID-IMMU2448>3.0.CO;2-N"},{"key":"2025092210500553000_12.9.ENEURO.0159-25.2025.4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.564965"},{"key":"2025092210500553000_12.9.ENEURO.0159-25.2025.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.04.005"},{"key":"2025092210500553000_12.9.ENEURO.0159-25.2025.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1741-3737.2012.01023.x"},{"key":"2025092210500553000_12.9.ENEURO.0159-25.2025.7","doi-asserted-by":"crossref","unstructured":"Frisbee JC , Brooks SD , Stanley SC , d'Audiffret AC (2015) An unpredictable chronic mild stress protocol for instigating depressive symptoms, behavioral changes and negative health outcomes in rodents. 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