Doxycycline effects in the haloperidol-induced tardive dyskinesia

• Grant number: 19/02300-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2019
• Effective date (End): December 10, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Elaine Aparecida Del Bel Belluz Guimarães
• Grantee: Rafaela Aparecida Ponciano da Silva de Moraes
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia, AP.TEM
• Associated scholarship(s): 19/14765-5 - The role of crosstalk between neurons and glia on experimental dopaminergic dysfunctions: how novelty in image analysis and glia to neuron exosome transfer can help us?, BE.EP.IC

Abstract

Schizophrenia is a chronic mental disorder characterized by positive symptoms (hallucinations, delusions, disordered thinking, and psychomotor agitation), negative symptoms (avolition, anhedonia, social isolation) and cognitive symptoms (deficits in memory and attention). The antipsychotics, classified as typical and atypical, show different efficacy to treat schizophrenia symptoms. Mostly, both classes can induce important side effects. Mainly, typical antipsychotics are responsible for the motor side effects. Tardive dyskinesia is one of the most relevant antipsychotic-induced motor side effects because of its potential irreversibility and prevalence rate among chronic patients exposed to high doses of antipsychotics. Tardive dyskinesia is characterized by involuntary and stereotyped orofacial movements that have large functional and social impact. The mechanisms enrolled in the tardive dyskinesia have not been fully elucidated. Probably, that there are (I) an increase in the D2-dopamine receptors sensitivity, because antipsychotics are antagonists of these receptors, and (II) the oxidative stress generated by the metabolism of the antipsychotic. New pharmacological uses have been suggested for the second generation of tetracyclines (minocycline and doxycycline), because they have anti-inflammatory, antioxidant and neuroprotective potential. Minocycline has shown beneficial results, especially in negative symptoms, in preclinical and clinical studies of schizophrenia. Doxycycline is well tolerated after prolonged sub-antibiotic treatment with no side effects. Thus, the objectives of this study are: (1) to investigate the potential of doxycycline for the tardive dyskinesia prevention, and (2) once confirmed, to evaluate through molecular techniques (zymography, reactive oxygen species -ROS- and succinate dehydrogenase activity -SDH detection) if these effects depend on doxycycline antioxidant action. The haloperidol decanoate-induced tardive dyskinesia is animal models that show predictive and face validity.