Tapentadol Prevents Motor Impairments in a Mouse Model of Dyskinesia

Publication date: Available online 1 November 2019Source: NeuroscienceAuthor(s): Rita L. Vaz, Diana Chapela, Joana E. Coelho, Luísa V. Lopes, Joaquim J. Ferreira, Nuno D. Afonso, Sara Sousa, Tiago F. OuteiroAbstractThe motor features in Parkinson’s disease (PD) are associated with the degeneration of dopaminergic cells in the substantia nigra in the brain. Thus, the gold-standard in PD therapeutics still consists of dopamine replacement with levodopa. However, as the disease progresses, this therapeutic option becomes less effective and can be accompanied by levodopa-induced complications. On the other hand, several other neuronal pathways have been implicated in the pathological mechanisms of PD. In this context, the development of alternative therapeutic options that modulate non-dopaminergic targets is emerging as a major goal in the field. In a phenotypic-based screen in a zebrafish model of PD, we identified tapentadol as a candidate molecule for PD. The therapeutic potential of an agent that modulates the opioid and noradrenergic systems has not been explored, despite the implication of both neuronal pathways in parkinsonism. Therefore, we assessed the therapeutic properties of this µ-opioid receptor agonist and norepinephrine reuptake inhibitor in the 6-hydroxydopamine mouse model of parkinsonism. We further submitted 6-hydroxydopamine-lesioned mice to chronic treatment with levodopa and evaluated the effects of tapentadol during levodopa OFF states and on levodopa...
Source: Neuroscience - Category: Neuroscience Source Type: research