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New therapeutic approaches that prevent or attenuate this side effect are needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p><jats:italic>Wistar<\/jats:italic> adult male rats submitted to 6\u2010hydroxydopamine\u2010induced unilateral medial forebrain bundle lesion were treated with <jats:sc>l<\/jats:sc>\u2010DOPA (p.o. 20\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> or s.c. 10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) once a day for 14\u2009days. After this period, we tested if doxycycline (40\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.p.) and COL\u20103 (50 and 100\u2009nmol, i.c.v.) could reverse <jats:sc>l<\/jats:sc>\u2010DOPA\u2010induced dyskinesia. In an additional experiment, doxycycline was administered together with <jats:sc>l<\/jats:sc>\u2010DOPA to verify if it would prevent <jats:sc>l<\/jats:sc>\u2010DOPA\u2010induced dyskinesia development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>A single injection of doxycycline or COL\u20103 attenuated <jats:sc>l<\/jats:sc>\u2010DOPA\u2010induced dyskinesia. Co\u2010treatment with doxycycline from the first day of <jats:sc>l<\/jats:sc>\u2010DOPA suppressed the onset of dyskinesia. The improved motor response after <jats:sc>l<\/jats:sc>\u2010DOPA was not affected by doxycycline or COL\u20103. Doxycycline treatment was associated with decreased immunoreactivity of FosB, COX\u20102, the astroglial protein GFAP and the microglial protein OX\u201042, which were elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline decreased metalloproteinase\u20102\/\u20109 activity, metalloproteinase\u20103 expression and ROS production. Metalloproteinase\u20102\/\u20109 activity and production of ROS in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The present study demonstrates the anti\u2010dyskinetic potential of doxycycline and its analogue compound COL\u20103 in hemiparkinsonian rats. Given the long\u2010established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or prevent <jats:sc>l<\/jats:sc>\u2010DOPA\u2010induced dyskinesia in Parkinson's patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15439","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T03:59:55Z","timestamp":1615348795000},"page":"2595-2616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Doxycycline and its derivative, COL\u20103, decrease dyskinesia induced by <scp>l<\/scp>\u2010DOPA in hemiparkinsonian rats"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0574-7456","authenticated-orcid":false,"given":"Mariza","family":"Bortolanza","sequence":"first","affiliation":[{"name":"Dental School of Ribeirao Preto University of Sao Paulo  Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5116-2200","authenticated-orcid":false,"given":"Glauce C.","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"Dental School of Ribeirao Preto University of Sao Paulo  Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4873-3935","authenticated-orcid":false,"given":"Rita","family":"Raisman\u2010Vozari","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, Inserm U 1127, CNRS UMR 7225 Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3483-8074","authenticated-orcid":false,"given":"Elaine","family":"Del\u2010Bel","sequence":"additional","affiliation":[{"name":"Dental School of Ribeirao Preto University of Sao Paulo  Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080776"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl224"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"issue":"1","key":"e_1_2_12_5_1","first-page":"S21","article-title":"The Concise Guide to PHARMACOLOGY 2019\/20: G protein\u2010coupled receptors","volume":"176","author":"Alexander S. 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