Sodium nitroprusside enhances stepping test performance and increases medium spiny neurons responsiveness to cortical inputs in a rat model of Levodopa-induced dyskinesias

Author(s)

Ribeiro, Danilo Leandro ; Guimaraes, Rayanne Poletti ; Bariotto-dos-Santos, Keila ; Del Bel, Elaine ; Padovan-Neto, Fernando E.

• Document type: Journal article
• Source: European Journal of Neuroscience; v. 59, n. 7, p. 17-pg., 2024-02-15.

Abstract

Levodopa (L-DOPA) is the classical gold standard treatment for Parkinson's disease. However, its chronic administration can lead to the development of L-DOPA-induced dyskinesias (LIDs). Dysregulation of the nitric oxide-cyclic guanosine monophosphate pathway in striatal networks has been linked to deficits in corticostriatal transmission in LIDs. This study investigated the effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on behavioural and electrophysiological outcomes in sham-operated and 6-hydroxydopamine-lesioned rats chronically treated with vehicle or L-DOPA, respectively. In sham-operated animals, systemic administration of SNP increased the spike probability of putative striatal medium spiny neurons (MSNs) in response to electrical stimulation of the primary motor cortex. In 6-hydroxydopamine-lesioned animals, SNP improved the stepping test performance without exacerbating abnormal involuntary movements. Additionally, SNP significantly increased the responsiveness of putative striatal MSNs in the dyskinetic striatum. These findings highlight the critical role of the NO signalling pathway in facilitating the responsiveness of striatal MSNs in both the intact and dyskinetic striata. The study suggests that SNP has the potential to enhance L-DOPA's effects in the stepping test without exacerbating abnormal involuntary movements, thereby offering new possibilities for optimizing Parkinson's disease therapy. In conclusion, this study highlights the involvement of the NO signalling pathway in the pathophysiology of LIDs. The NO donor sodium nitroprusside (SNP) improved the stepping test performance without exacerbating abnormal involuntary movements (AIMs) in 6-hydroxydopamine (6-OHDA)-lesioned rats. Furthermore, SNP facilitated cortically evoked spike activity in dyskinetic animals. These results suggest that NO-cGMP signalling in the striatum is likely linked to the pathophysiology of hyperkinetic movement disorders. image (AU)

• FAPESP's process: 19/24392-1 - Role of neuronal nitric oxide synthase and phosphodiesterase 10A in striatal medium spiny neuron activity during L-DOPA-induced dyskinesia
• Grantee: Keila Dayane Bariotto dos Santos
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 19/04188-0 - Role of neuronal nitric oxide synthase in striatal medium spiny neuron activity during the occurrence of L-DOPA-induced dyskinesia
• Grantee: Danilo Leandro Ribeiro
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/00003-0 - Role of neuronal nitric oxide synthase and phosphodiesterase 10A in striatal medium spiny neuron activity during L-Dopa-induced dyskinesia
• Grantee: Fernando Eduardo Padovan Neto
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/12956-5 - Role of phosphodiesterase 10A in striatal medium spiny neuron activity during L-DOPA-induced dyskinesia
• Grantee: Rayanne Poletti Guimarães
• Support Opportunities: Scholarships in Brazil - Master