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The "motor complication syndrome" in rats with 6-OHDA lesions treated chronically with l-DOPA: Relation to dose and route of administration.

Lindgren, Hanna LU ; Rylander, Daniella LU ; Ohlin, Elisabet LU ; Lundblad, Martin LU and Cenci Nilsson, Angela LU (2007) In Behavioural Brain Research 177(1). p.150-159
Abstract
l-DOPA-induced motor complications can be modelled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injections of l-DOPA. We have compared the sensitisation and duration of rotational responses, and the occurrence of dose–failure episodes and abnormal involuntary movements (AIMs) in 6-OHDA-lesioned rats with regard to the dose and route of administration of l-DOPA. Rats were treated with either low (6 mg/kg) or high (25 mg/kg) doses of l-DOPA twice daily for 21 days whereas control animals received injections of either saline or bromocriptine (2.5 mg/kg). A dose-dependent and gradual development of AIMs and contralateral turning was observed in rats treated chronically with l-DOPA. Rats treated with bromocriptine exhibited... (More)
l-DOPA-induced motor complications can be modelled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injections of l-DOPA. We have compared the sensitisation and duration of rotational responses, and the occurrence of dose–failure episodes and abnormal involuntary movements (AIMs) in 6-OHDA-lesioned rats with regard to the dose and route of administration of l-DOPA. Rats were treated with either low (6 mg/kg) or high (25 mg/kg) doses of l-DOPA twice daily for 21 days whereas control animals received injections of either saline or bromocriptine (2.5 mg/kg). A dose-dependent and gradual development of AIMs and contralateral turning was observed in rats treated chronically with l-DOPA. Rats treated with bromocriptine exhibited rotational sensitisation but no AIMs. A shortening of motor response duration was not seen in any of the drug-treated groups. In contrast, dose–failure episodes occurred frequently in both l-DOPA- and bromocriptine-treated animals. Changing the route of l-DOPA administration from intraperitoneal to subcutaneous completely abolished failures in motor response without affecting the development of dyskinesia. Based on the hypothesis that higher doses of l-DOPA may be toxic to dopaminoceptive structures, we compared the total number of neurons and the levels of activated microglia in the striatum. No signs of neurodegenerative changes could be seen in any of the treatment groups. In conclusion, both body AIMs and rotations were dose-dependently evoked by l-DOPA. Only AIMs, however, provided a specific measure of dyskinesia since rotations also were induced by bromocriptine, a drug with low dyskinesiogenic potential. Dose–failure episodes were not specific to l-DOPA treatment and could be attributed to erratic drug absorption from the peritoneal route. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Striatum, Toxicity, Motor complications, Parkinson's disease, l-DOPA, 6-OHDA
in
Behavioural Brain Research
volume
177
issue
1
pages
150 - 159
publisher
Elsevier
external identifiers
  • wos:000244129000019
  • scopus:33845976016
ISSN
0166-4328
DOI
10.1016/j.bbr.2006.09.019
language
English
LU publication?
yes
id
cf330ad8-236d-4434-aafc-d5f020e7612c (old id 164130)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17157933&dopt=Abstract
date added to LUP
2007-07-16 16:08:11
date last changed
2017-11-05 03:44:40
@article{cf330ad8-236d-4434-aafc-d5f020e7612c,
  abstract     = {l-DOPA-induced motor complications can be modelled in rats with 6-hydroxydopamine (6-OHDA) lesions by chronic injections of l-DOPA. We have compared the sensitisation and duration of rotational responses, and the occurrence of dose–failure episodes and abnormal involuntary movements (AIMs) in 6-OHDA-lesioned rats with regard to the dose and route of administration of l-DOPA. Rats were treated with either low (6 mg/kg) or high (25 mg/kg) doses of l-DOPA twice daily for 21 days whereas control animals received injections of either saline or bromocriptine (2.5 mg/kg). A dose-dependent and gradual development of AIMs and contralateral turning was observed in rats treated chronically with l-DOPA. Rats treated with bromocriptine exhibited rotational sensitisation but no AIMs. A shortening of motor response duration was not seen in any of the drug-treated groups. In contrast, dose–failure episodes occurred frequently in both l-DOPA- and bromocriptine-treated animals. Changing the route of l-DOPA administration from intraperitoneal to subcutaneous completely abolished failures in motor response without affecting the development of dyskinesia. Based on the hypothesis that higher doses of l-DOPA may be toxic to dopaminoceptive structures, we compared the total number of neurons and the levels of activated microglia in the striatum. No signs of neurodegenerative changes could be seen in any of the treatment groups. In conclusion, both body AIMs and rotations were dose-dependently evoked by l-DOPA. Only AIMs, however, provided a specific measure of dyskinesia since rotations also were induced by bromocriptine, a drug with low dyskinesiogenic potential. Dose–failure episodes were not specific to l-DOPA treatment and could be attributed to erratic drug absorption from the peritoneal route.},
  author       = {Lindgren, Hanna and Rylander, Daniella and Ohlin, Elisabet and Lundblad, Martin and Cenci Nilsson, Angela},
  issn         = {0166-4328},
  keyword      = {Striatum,Toxicity,Motor complications,Parkinson's disease,l-DOPA,6-OHDA},
  language     = {eng},
  number       = {1},
  pages        = {150--159},
  publisher    = {Elsevier},
  series       = {Behavioural Brain Research},
  title        = {The "motor complication syndrome" in rats with 6-OHDA lesions treated chronically with l-DOPA: Relation to dose and route of administration.},
  url          = {http://dx.doi.org/10.1016/j.bbr.2006.09.019},
  volume       = {177},
  year         = {2007},
}