Abstract
In Parkinson’s disease (PD), dyskinesia is a consequence of nigral dopaminergic cell death and chronic levodopa treatment. The cause of levodopa-induced dyskinesia (LID) is unknown but may result from adaptive neuronal changes in the striatum (1). In PD, as well as rodents with an unilateral median forebrain bundle lesion, expression of nNOS mRNA, as well the number of nNOS immunoreactive (-ir) neurones is markedly altered and nNOS inhibitors can reduce levodopa-induced motor abnormalities (2).
We counted the number of neuronal nitric oxide synthase immunoreactive (nNOS-ir) interneurones in the caudate nucleus (CN) and putamen (PUT) in normal, drug naïve, common marmosets (n=6) compared to MPTP-treated animals (0.2mg/kg/day, s.c. for 5 consecutive days) that were chronically treated with levodopa (8 mg/kg levodopa plus 10 mg/kg benserazide) but expressed little dyskinesia (n=6) and those that expressed marked dyskinesia (n=7). In the low dyskinesia group (n=6), peak dyskinesia rarely exceeded score 1 and the high dyskinesia group (n=7) scores were >2. The animals were euthanized by pentobarbital sodium (60 mg/kg), and perfuse fixed with 4% paraformaldehyde. Striatal and nigral sections (30 μm) were processed for immunoperoxidase staining for nNOS-ir and tyrosine hydroxylase immunoreactivity (TH-ir) in substantia nigra (SN) and striatum respectively.
We counted the number of neuronal nitric oxide synthase immunoreactive (nNOS-ir) interneurones in the caudate nucleus (CN) and putamen (PUT) in normal, drug naïve, common marmosets (n=6) compared to MPTP-treated animals (0.2mg/kg/day, s.c. for 5 consecutive days) that were chronically treated with levodopa (8 mg/kg levodopa plus 10 mg/kg benserazide) but expressed little dyskinesia (n=6) and those that expressed marked dyskinesia (n=7). In the low dyskinesia group (n=6), peak dyskinesia rarely exceeded score 1 and the high dyskinesia group (n=7) scores were >2. The animals were euthanized by pentobarbital sodium (60 mg/kg), and perfuse fixed with 4% paraformaldehyde. Striatal and nigral sections (30 μm) were processed for immunoperoxidase staining for nNOS-ir and tyrosine hydroxylase immunoreactivity (TH-ir) in substantia nigra (SN) and striatum respectively.
Original language | English |
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Article number | 219P |
Number of pages | 2 |
Journal | pA2 online |
Volume | 11 |
Issue number | 3 |
Publication status | Published - 2013 |
Event | Pharmacology 2013 [BPS Winter Meeting] - London, United Kingdom Duration: 17 Dec 2013 → 19 Dec 2013 |