| Full text | |
| Author(s): |
Bortolanza, Mariza
[1]
;
do Nascimento, Glauce C.
[1]
;
Raisman-Vozari, Rita
[2]
;
Del-Bel, Elaine
[1]
Total Authors: 4
|
| Affiliation: | [1] Univ Sao Paulo, Dent Sch Ribeirao Preto, Ribeirao Preto - Brazil
[2] Sorbonne Univ, Paris Brain Inst, Inserm U1127, CNRS UMR 7225, Paris - France
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | British Journal of Pharmacology; v. 178, n. 13 APR 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
Background and Purpose l-DOPA-induced dyskinesia is a debilitating effect of treating Parkinson's disease with this drug. New therapeutic approaches that prevent or attenuate this side effect are needed. Experimental Approach Wistar adult male rats submitted to 6-hydroxydopamine-induced unilateral medial forebrain bundle lesion were treated with l-DOPA (p.o. 20 mg center dot kg(-1) or s.c. 10 mg center dot kg(-1)) once a day for 14 days. After this period, we tested if doxycycline (40 mg center dot kg(-1), i.p.) and COL-3 (50 and 100 nmol, i.c.v.) could reverse l-DOPA-induced dyskinesia. In an additional experiment, doxycycline was administered together with l-DOPA to verify if it would prevent l-DOPA-induced dyskinesia development. Key Results A single injection of doxycycline or COL-3 attenuated l-DOPA-induced dyskinesia. Co-treatment with doxycycline from the first day of l-DOPA suppressed the onset of dyskinesia. The improved motor response after l-DOPA was not affected by doxycycline or COL-3. Doxycycline treatment was associated with decreased immunoreactivity of FosB, COX-2, the astroglial protein GFAP and the microglial protein OX-42, which were elevated in the basal ganglia of rats exhibiting dyskinesia. Doxycycline decreased metalloproteinase-2/-9 activity, metalloproteinase-3 expression and ROS production. Metalloproteinase-2/-9 activity and production of ROS in the basal ganglia of dyskinetic rats showed a significant correlation with the intensity of dyskinesia. Conclusion and Implications The present study demonstrates the anti-dyskinetic potential of doxycycline and its analogue compound COL-3 in hemiparkinsonian rats. Given the long-established and safe clinical use of doxycycline, this study suggests that these drugs might be tested to reduce or prevent l-DOPA-induced dyskinesia in Parkinson's patients. (AU) | |
| FAPESP's process: | 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia |
| Grantee: | Elaine Aparecida Del Bel Belluz Guimarães |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders |
| Grantee: | Francisco Silveira Guimaraes |
| Support Opportunities: | Research Projects - Thematic Grants |