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Nefazodone reduces dyskinesia, but not psychosis-like behaviours, in the parkinsonian marmoset.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2018 Dec; Vol. 391 (12), pp. 1339-1345. Date of Electronic Publication: 2018 Aug 07. - Publication Year :
- 2018
-
Abstract
- Nefazodone is an anti-depressant that interacts with a wealth of pharmacological targets, including some that may exert anti-dyskinetic and anti-psychotic effects in Parkinson's disease (PD), notably serotonin 1A and 2A receptors. In this study, we sought to determine the effect of nefazodone on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia and psychosis-like behaviours (PLBs) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate. Six common marmosets developed parkinsonism following administration of MPTP, after which they were treated chronically with L-DOPA to induce stable dyskinesia and PLBs. In behavioural experiments, nefazodone (0.01, 0.1 and 1 mg/kg) or vehicle was administered in combination with L-DOPA and its effects on dyskinesia, PLBs and parkinsonian disability were assessed. The addition of nefazodone 0.01, 0.1 and 1 mg/kg to L-DOPA reduced the severity of peak dose dyskinesia by ≈ 21%, ≈ 39% and ≈ 42% (all P < 0.05), while it did not have any significant effect on PLBs, when compared to L-DOPA/vehicle. Parkinsonian disability was not affected by any dose of nefazodone. Our results suggest that nefazodone may be effective to alleviate L-DOPA-induced dyskinesia in PD, while it may not exert any beneficial effect on dopaminergic psychosis.
- Subjects :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Behavior, Animal drug effects
Callithrix
Female
Levodopa
Male
Antiparkinson Agents therapeutic use
Dyskinesia, Drug-Induced drug therapy
Parkinsonian Disorders drug therapy
Piperazines therapeutic use
Psychoses, Substance-Induced drug therapy
Triazoles therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1912
- Volume :
- 391
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 30088028
- Full Text :
- https://doi.org/10.1007/s00210-018-1549-6