Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats
(2012) In Neuropharmacology 63(5). p.28-818- Abstract
Foetal cell transplantation in patients with Parkinson's disease can induce motor complications independent of L-DOPA administration, known as graft-induced dyskinesia. In the 6-OHDA lesioned rat model of Parkinson's disease, post-transplantation abnormal movements can develop in response to an amphetamine challenge, a behaviour which is used to model graft-induced dyskinesia. Although L-DOPA-induced dyskinesia has been well characterised pharmacologically, we lack knowledge on the modulation of post-transplantation amphetamine-induced dyskinesia which may shed light on the mechanisms underlying graft-induced dyskinesia. We assessed a series of drugs effective at reducing L-DOPA-induced dyskinesia against post-transplantation... (More)
Foetal cell transplantation in patients with Parkinson's disease can induce motor complications independent of L-DOPA administration, known as graft-induced dyskinesia. In the 6-OHDA lesioned rat model of Parkinson's disease, post-transplantation abnormal movements can develop in response to an amphetamine challenge, a behaviour which is used to model graft-induced dyskinesia. Although L-DOPA-induced dyskinesia has been well characterised pharmacologically, we lack knowledge on the modulation of post-transplantation amphetamine-induced dyskinesia which may shed light on the mechanisms underlying graft-induced dyskinesia. We assessed a series of drugs effective at reducing L-DOPA-induced dyskinesia against post-transplantation amphetamine-induced dyskinesia. Agents include: dopaminergic antagonists (D₁: CP94253; D₂: SCH-22390; D₃: nafadotride), serotonergic agonists (5-HT(1A): 8-OH-DPAT; 5-HT(1B): CP94253), opioid antagonist (μ: naloxone), cannabinoid agonist (CB₁: WIN55, 212-2), adrenergic antagonist (α₁ and α₂: yohimbine) and glutamatergic antagonists (NMDA: amantadine and MK-801; mGluR5: MTEP; AMPA: IEM1460). Abnormal involuntary movements in response to amphetamine were decreased by SCH-22390, raclopride, CP94253 and 8-OH-DPAT, yet were unaltered by naloxone, WIN55, 212-2, yohimbine, amantadine, MTEP and IEM1460. Unusually, MK-801 increased the appearance of amphetamine-induced dyskinesia. The results suggest that dopaminergic, serotoninergic and glutamatergic systems are likely to have a fundamental role in the development of graft-induced dyskinesias, which are mechanistically distinct from L-DOPA-induced behvaviours. Importantly, the expression of D₁ and D₂ receptors was unrelated to the severity of AIMs.
(Less)
- author
- Smith, Gaynor A ; Breger, Ludivine S LU ; Lane, Emma L LU and Dunnett, Stephen B
- publishing date
- 2012-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Anti-Dyskinesia Agents, Cell Transplantation, Disease Models, Animal, Dopamine Antagonists, Dopamine Uptake Inhibitors, Dose-Response Relationship, Drug, Dyskinesia, Drug-Induced, Dyskinesias, Excitatory Amino Acid Antagonists, Female, Mesencephalon, Methamphetamine, Neostriatum, Nerve Tissue Proteins, Neurons, Parkinson Disease, Random Allocation, Rats, Rats, Sprague-Dawley, Receptors, Neurotransmitter, Serotonin Receptor Agonists, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- in
- Neuropharmacology
- volume
- 63
- issue
- 5
- pages
- 11 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:22722025
- scopus:84864425280
- ISSN
- 1873-7064
- DOI
- 10.1016/j.neuropharm.2012.06.011
- language
- English
- LU publication?
- no
- id
- 84fe45fe-d152-4288-98d3-1704911628f0
- date added to LUP
- 2016-10-04 13:20:53
- date last changed
- 2024-01-04 13:47:14
@article{84fe45fe-d152-4288-98d3-1704911628f0,
abstract = {{<p>Foetal cell transplantation in patients with Parkinson's disease can induce motor complications independent of L-DOPA administration, known as graft-induced dyskinesia. In the 6-OHDA lesioned rat model of Parkinson's disease, post-transplantation abnormal movements can develop in response to an amphetamine challenge, a behaviour which is used to model graft-induced dyskinesia. Although L-DOPA-induced dyskinesia has been well characterised pharmacologically, we lack knowledge on the modulation of post-transplantation amphetamine-induced dyskinesia which may shed light on the mechanisms underlying graft-induced dyskinesia. We assessed a series of drugs effective at reducing L-DOPA-induced dyskinesia against post-transplantation amphetamine-induced dyskinesia. Agents include: dopaminergic antagonists (D₁: CP94253; D₂: SCH-22390; D₃: nafadotride), serotonergic agonists (5-HT(1A): 8-OH-DPAT; 5-HT(1B): CP94253), opioid antagonist (μ: naloxone), cannabinoid agonist (CB₁: WIN55, 212-2), adrenergic antagonist (α₁ and α₂: yohimbine) and glutamatergic antagonists (NMDA: amantadine and MK-801; mGluR5: MTEP; AMPA: IEM1460). Abnormal involuntary movements in response to amphetamine were decreased by SCH-22390, raclopride, CP94253 and 8-OH-DPAT, yet were unaltered by naloxone, WIN55, 212-2, yohimbine, amantadine, MTEP and IEM1460. Unusually, MK-801 increased the appearance of amphetamine-induced dyskinesia. The results suggest that dopaminergic, serotoninergic and glutamatergic systems are likely to have a fundamental role in the development of graft-induced dyskinesias, which are mechanistically distinct from L-DOPA-induced behvaviours. Importantly, the expression of D₁ and D₂ receptors was unrelated to the severity of AIMs.</p>}},
author = {{Smith, Gaynor A and Breger, Ludivine S and Lane, Emma L and Dunnett, Stephen B}},
issn = {{1873-7064}},
keywords = {{Animals; Anti-Dyskinesia Agents; Cell Transplantation; Disease Models, Animal; Dopamine Antagonists; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Dyskinesias; Excitatory Amino Acid Antagonists; Female; Mesencephalon; Methamphetamine; Neostriatum; Nerve Tissue Proteins; Neurons; Parkinson Disease; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Neurotransmitter; Serotonin Receptor Agonists; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
number = {{5}},
pages = {{28--818}},
publisher = {{Elsevier}},
series = {{Neuropharmacology}},
title = {{Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats}},
url = {{http://dx.doi.org/10.1016/j.neuropharm.2012.06.011}},
doi = {{10.1016/j.neuropharm.2012.06.011}},
volume = {{63}},
year = {{2012}},
}