Session Information
Date: Monday, September 23, 2019
Session Title: Neuropharmacology
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To investigate the effects of safinamide (saf) on synaptic plasticity of spiny projection neurons (SPNs) and the antiparkinsonian effect in dopamine (DA) denervated rats co-administered with levodopa (L-DOPA).
Background: Current therapeutic options for Parkinson’s disease (PD) are primarily DA replacement strategies that, however, can progressively cause motor fluctuations and L-DOPA-induced dyskinesia (LID). DA-denervation causes loss of striatal bidirectional synaptic plasticity (long term potentiation, LTP and long term depression, LTD). Chronic treatment with L-DOPA can restore LTP but can be associated with loss of depotentiation in dyskinetic animals.
Method: Saf effects on synaptic plasticity were investigated ex vivo by patch-clamp recordings in striatal slices of naïve rats and DA-denervated rats treated with 6mg/Kg L-DOPA+12mg/Kg benserazide once a day for 3 weeks. In vivo LID was assessed in the absence or presence of 15mg/Kg chronic saf (30 min before administration of L-DOPA) and measured by scoring abnormal involuntary movements (AIMs). Motor deficit quantification was evaluated with the stepping test.
Results: Saf 3 microM, did not affect either LTP or LTD in naïve rats. Chronic co-administration of saf+L-DOPA did not affect the L-DOPA-induced LTP recovery but a higher percentage of cells (80%) displaying LTP in L-DOPA+saf rats was found compared to rats treated with L-DOPA alone (67%). Moreover, SPNs of L-DOPA+saf-treated rats showed almost complete recovery of depotentiation. Although saf had no effect on AIMs, the trend in ameliorating depontentiation was paralleled by improvement of motor behavior at the stepping test before the onset of LID (conta/ipsi adjusting steps, pre-treatment =0.23, post-treatment=0.78, p<0.01).
Conclusion: Saf, at a therapeutically relevant concentration range, did not affect LTD or LTP in naïve rats. Co-administration of saf with L-DOPA did not affect L-DOPA-induced LTP recovery but promoted depotentiation with a parallel improvement in motor deficit.
To cite this abstract in AMA style:
M. Sciaccaluga, P. Mazzocchetti, G. Bastioli, V. Ghiglieri, B. Picconi, A. Tozzi, C. Caccia, C. Keywood, G. Padoani, P. Calabresi. Safinamide ameliorates motor deficits and plastic alterations before the onset of L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/safinamide-ameliorates-motor-deficits-and-plastic-alterations-before-the-onset-of-l-dopa-induced-dyskinesia-in-a-rat-model-of-parkinsons-disease/. Accessed June 14, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/safinamide-ameliorates-motor-deficits-and-plastic-alterations-before-the-onset-of-l-dopa-induced-dyskinesia-in-a-rat-model-of-parkinsons-disease/