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Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats

Smith, Gaynor A., Breger, Ludivine S., Lane, Emma Louise and Dunnett, Stephen Bruce 2012. Pharmacological modulation of amphetamine-induced dyskinesia in transplanted hemi-parkinsonian rats. Neuropharmacology 63 (5) , pp. 818-828. 10.1016/j.neuropharm.2012.06.011

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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 amphetamine-induced dyskinesia. Agents include: dopaminergic antagonists (D1: CP94253; D2: SCH-22390; D3: nafadotride), serotonergic agonists (5-HT1A: 8-OH-DPAT; 5-HT1B: 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Pharmacy
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: L-3,4-dihydroxyphenylalanine; Dyskinesia; Graft; Methamphetamine; Dopamine; Receptors
Publisher: Elsevier
ISSN: 0028-3908
Last Modified: 11 Apr 2019 22:11
URI: http://orca.cf.ac.uk/id/eprint/41691

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