Source Paper
Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test
M Olsson, G Nikkhah, C Bentlage, A Bjorklund
Journal of Neuroscience • 1995
Source Paper
M Olsson, G Nikkhah, C Bentlage, A Bjorklund
Journal of Neuroscience • 1995
Methods for the assessment of akinesia in the unilateral rat Parkinson model have so far been lacking. The experiments reported here evaluate the usefulness of a new “stepping test” to monitor forelimb akinesia in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesencephalic dopamine (DA) system, and to assess the ability of DA- receptor agonists and fetal DA neuron transplants to reverse these deficits. The 6-OHDA lesion induced marked and long-lasting impairments in the initiation of stepping movements with the contralateral paw. Systemic injections of low doses (chosen to be subthreshold for induction of rotation) of the mixed D1 and D2 receptor agonist apomorphine, the D1-selective agonist SKF 38393, and to a lesser extent also the D2-selective agonist quinpirole were effective in reversing these deficits. Similar effects was seen after a subrotational dose of L-dopa, whereas amphetamine had no effect. Fetal nigral transplants, implanted as multiple deposits in the ipsilateral caudate-putamen and substantia nigra, restored initiation of stepping to a similar degree as the DA agonists. Nigral grafts placed in substantia nigra alone were also effective, although the improvement was less pronounced. Apomorphine, at a dose effective in the lesion-only animals, had no additive effect in the grafted rats, whereas amphetamine appeared to further improve stepping in the rats with intranigral transplants. Identical experiments were performed on skilled forelimb use in the so- called staircase test. Interestingly, neither the DA agonist drugs nor the nigral transplants had any effects on the lesion induced deficits in this more complex task. The results show that forelimb stepping is a highly useful test to monitor lesion-/and transplant-induced changes in forelimb akinesia, a behavioral parameter that may be analogous to limb akinesia and gait problems seen in patients with Parkinson's disease.
Objective: To assess forelimb akinesia and stepping movements in rats with unilateral 6-OHDA lesions of the dopamine system, and to evaluate the effectiveness of dopamine agonists and fetal dopamine neuron transplants in reversing these deficits
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Induce unilateral 6-hydroxydopamine lesion of the mesencephalic dopamine system in rats
Note: This creates the Parkinson model with marked and long-lasting impairments in stepping movements with the contralateral paw
“The 6-OHDA lesion induced marked and long-lasting impairments in the initiation of stepping movements with the contralateral paw”
Systemically inject low doses of apomorphine (mixed D1 and D2 receptor agonist) chosen to be subthreshold for induction of rotation
Note: Apomorphine was effective in reversing stepping deficits
“Systemic injections of low doses (chosen to be subthreshold for induction of rotation) of the mixed D1 and D2 receptor agonist apomorphine”
Systemically inject low doses of SKF 38393 (D1-selective agonist) chosen to be subthreshold for induction of rotation
Note: SKF 38393 was effective in reversing stepping deficits
“the D1-selective agonist SKF 38393, and to a lesser extent also the D2-selective agonist quinpirole were effective in reversing these deficits”
Systemically inject low doses of quinpirole (D2-selective agonist) chosen to be subthreshold for induction of rotation
Note: Quinpirole was less effective than D1-selective agonist but still effective in reversing stepping deficits
“the D2-selective agonist quinpirole were effective in reversing these deficits”
Systemically inject a subrotational dose of L-dopa
Note: Similar effects to dopamine agonists were observed
“Similar effects was seen after a subrotational dose of L-dopa”
Systemically inject amphetamine
Note: Amphetamine had no effect on stepping deficits in lesion-only animals but appeared to further improve stepping in rats with intranigral transplants
“whereas amphetamine had no effect”
Implant fetal dopamine neuron transplants as multiple deposits in the ipsilateral caudate-putamen and substantia nigra
Note: Transplants restored initiation of stepping to a similar degree as dopamine agonists
“Fetal nigral transplants, implanted as multiple deposits in the ipsilateral caudate-putamen and substantia nigra, restored initiation of stepping”
Implant fetal dopamine neuron transplants in substantia nigra alone as an alternative placement
Note: Nigral grafts placed in substantia nigra alone were also effective, although improvement was less pronounced than multiple deposits
“Nigral grafts placed in substantia nigra alone were also effective, although the improvement was less pronounced”
Administer apomorphine at a dose effective in lesion-only animals to rats with nigral transplants
Note: Apomorphine had no additive effect in grafted rats
“Apomorphine, at a dose effective in the lesion-only animals, had no additive effect in the grafted rats”
Administer amphetamine to rats with intranigral transplants
Note: Amphetamine appeared to further improve stepping in rats with intranigral transplants
“amphetamine appeared to further improve stepping in the rats with intranigral transplants”
Conduct identical experiments on skilled forelimb use using the staircase test as a comparison task
Note: Neither dopamine agonist drugs nor nigral transplants had any effects on lesion-induced deficits in this more complex task
“Identical experiments were performed on skilled forelimb use in the so-called staircase test”
Monitor and assess forelimb stepping movements during the stepping test
Note: The stepping test is a highly useful test to monitor lesion- and transplant-induced changes in forelimb akinesia
“forelimb stepping is a highly useful test to monitor lesion-/and transplant-induced changes in forelimb akinesia”
Rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesencephalic dopamine system