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Does contraversive circling in the 6-OHDA-lesioned rat indicate an ability to induce motor complications as well as therapeutic effects in Parkinson's disease?

Lane, Emma LU ; Cheetham, SC and Jenner, P (2006) In Experimental Neurology 197(2). p.284-290
Abstract
Circling behaviour in unilateral 6-OHDA-lesioned rats is interpreted as being opposite in direction to the side of the brain with highest striatal dopaminergic activation. Ipsiversive rotation indicates an action on the intact striatum, while contraversive rotation demonstrates an effect on dopamine receptors in the denervated striatum and is taken as predictive of symptomatic benefit in Parkinson's disease. But does an equivalent behavioural outcome result from stimulating the intact and denervated striatum to the same degree? We report on the behavioural responses produced by administration of L-dopa and the monoamine uptake inhibitor BTS 74 398. These were given alone, or in combination, at doses equivalent to their ED25, ED50 and ED75... (More)
Circling behaviour in unilateral 6-OHDA-lesioned rats is interpreted as being opposite in direction to the side of the brain with highest striatal dopaminergic activation. Ipsiversive rotation indicates an action on the intact striatum, while contraversive rotation demonstrates an effect on dopamine receptors in the denervated striatum and is taken as predictive of symptomatic benefit in Parkinson's disease. But does an equivalent behavioural outcome result from stimulating the intact and denervated striatum to the same degree? We report on the behavioural responses produced by administration of L-dopa and the monoamine uptake inhibitor BTS 74 398. These were given alone, or in combination, at doses equivalent to their ED25, ED50 and ED75 for inducing circling in unilateral 6-OHDA-lesioned rats. L-dopa administered alone induced dose-dependent contraversive circling while BTS 74 398 produced ipsiversive rotation. However, L-dopa and BTS 74 398 in combination, produced the same contraversive circling response as when L-dopa was administered alone. Little or no ipsiversive rotation occurred, irrespective of the combination of doses employed. This surprising finding suggests that there are major differences in the outcome of stimulating the intact and denervated striatum with the latter dominating the behavioural response. Since repeated administration Of L-dopa but not BTS 74 398, sensitises rotational responses and induces abnormal movements, it may be that contraversive rotation is predictive of both clinical response in PD and the ability to induce motor complications. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
L-dopa, behaviour, monoannine reuptake inhibitor, Parkinson's disease
in
Experimental Neurology
volume
197
issue
2
pages
284 - 290
publisher
Elsevier
external identifiers
  • wos:000235131000003
  • pmid:16005456
  • scopus:30444449968
  • pmid:16005456
ISSN
0014-4886
DOI
10.1016/j.expneurol.2005.06.006
language
English
LU publication?
yes
id
bd09e81f-04a0-4923-a0d0-da2d4e045e39 (old id 418219)
date added to LUP
2016-04-01 12:02:13
date last changed
2022-03-28 19:17:49
@article{bd09e81f-04a0-4923-a0d0-da2d4e045e39,
  abstract     = {{Circling behaviour in unilateral 6-OHDA-lesioned rats is interpreted as being opposite in direction to the side of the brain with highest striatal dopaminergic activation. Ipsiversive rotation indicates an action on the intact striatum, while contraversive rotation demonstrates an effect on dopamine receptors in the denervated striatum and is taken as predictive of symptomatic benefit in Parkinson's disease. But does an equivalent behavioural outcome result from stimulating the intact and denervated striatum to the same degree? We report on the behavioural responses produced by administration of L-dopa and the monoamine uptake inhibitor BTS 74 398. These were given alone, or in combination, at doses equivalent to their ED25, ED50 and ED75 for inducing circling in unilateral 6-OHDA-lesioned rats. L-dopa administered alone induced dose-dependent contraversive circling while BTS 74 398 produced ipsiversive rotation. However, L-dopa and BTS 74 398 in combination, produced the same contraversive circling response as when L-dopa was administered alone. Little or no ipsiversive rotation occurred, irrespective of the combination of doses employed. This surprising finding suggests that there are major differences in the outcome of stimulating the intact and denervated striatum with the latter dominating the behavioural response. Since repeated administration Of L-dopa but not BTS 74 398, sensitises rotational responses and induces abnormal movements, it may be that contraversive rotation is predictive of both clinical response in PD and the ability to induce motor complications.}},
  author       = {{Lane, Emma and Cheetham, SC and Jenner, P}},
  issn         = {{0014-4886}},
  keywords     = {{L-dopa; behaviour; monoannine reuptake inhibitor; Parkinson's disease}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{284--290}},
  publisher    = {{Elsevier}},
  series       = {{Experimental Neurology}},
  title        = {{Does contraversive circling in the 6-OHDA-lesioned rat indicate an ability to induce motor complications as well as therapeutic effects in Parkinson's disease?}},
  url          = {{http://dx.doi.org/10.1016/j.expneurol.2005.06.006}},
  doi          = {{10.1016/j.expneurol.2005.06.006}},
  volume       = {{197}},
  year         = {{2006}},
}