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

Gaynor A. Smith, Ludivine S. Breger, Emma L. Lane, Stephen B. Dunnett
Neuropharmacology. 2012-10-01; 63(5): 818-828
DOI: 10.1016/j.neuropharm.2012.06.011

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1. Neuropharmacology. 2012 Oct;63(5):818-28. doi: 10.1016/j.neuropharm.2012.06.011.
Epub 2012 Jun 18.

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

Smith GA(1), Breger LS, Lane EL, Dunnett SB.

Author information:
(1)Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales,

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.

Copyright © 2012 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.neuropharm.2012.06.011
PMID: 22722025 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus