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. 2022 Apr 25;13:863959. doi: 10.3389/fphar.2022.863959

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Copyright © 2022 Bifari, Pappagallo, Bleavins, Traversa, Folli and Manfredi.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Administration of REL-1017 did not cause microgliosis in the brain cingulate cortex. (A) Immunohistochemistry analysis of IBA1 positive (brown) microglial cells in the cingulate cortex at Day 3 and 5. MK-801 treated samples showed a clear increase in IBA1 positive (brown) microglial cells. (B) Quantification of microgliosis. The oral administration of REL-1017 at any dose (low, mid, and high) and of methadone racemate to both male and female Sprague-Dawley rats did not induce microgliosis (p = ns versus all other groups). Statistical increase in microglia cell number, sored as mild microgliosis, were observed in animals treated with MK-801 at Day 3 (p < 0.0001) and 5 (p < 0.0001) compared to all the other groups.