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Among various pathological conditions underlying spasticity, upregulated expression of 5-HT receptors (5-HTR) on the spinal motor neurons due to 5-HT denervation is considered one of crucial factors for hyperexcitability of the spinal circuit. As a 5-HT signal modulator, selective serotonin re-uptake inhibitors (SSRIs) are ordinarily prescribed for diseases associated with 5-HT in the CNS, and are known for their ability to increase 5-HT levels as well as to desensitize 5-HTR. Here, we hypothesized that early SSRI administration as a preemptive treatment strategy would effectively prevent the onset of spasticity. We used a rat model of contusive SCI and administered escitalopram during the first 4\u00a0weeks after injury, which is the period required for spasticity development in rodent models. We performed a swimming test to quantify spastic behaviors and conducted the Hoffman reflex test as well as histological analyses for 5-HT<jats:sub>2A<\/jats:sub>R and KCC2 expressions. Four weeks of escitalopram administration suppressed spastic behaviors during the swimming test and reduced the population of spasticity-strong rats. Moreover, the treatment resulted in decreased immunoreactivity of 5-HT<jats:sub>2A<\/jats:sub>R in the spinal motor neurons. Result of the H-reflex test and membrane expression of KCC2 were not significantly altered. In summary, early escitalopram administration could prevent the onset of spastic behaviors via regulation of 5-HT system after SCI, but could not modulate exaggerated spinal reflex. Our results suggest a novel application of SSRIs for preventative treatment of spasticity.<\/jats:p>","DOI":"10.1038\/s41598-021-85961-5","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T10:03:03Z","timestamp":1617012183000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Early escitalopram administration as a preemptive treatment strategy against spasticity after contusive spinal cord injury in rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Youngjae","family":"Ryu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoshi","family":"Nagao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Sawada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryohei","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"85961_CR1","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/sj.sc.3101757","volume":"43","author":"MM Adams","year":"2005","unstructured":"Adams, M. 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