Chronic levodopa therapy does not improve skilled reach accuracy or reach range on a pasta matrix reaching task in 6‐OHDA dopamine‐depleted (hemi‐Parkinson analogue) rats

Abstract

L-dopa therapy reverses some but not all of the motor deficits in human Parkinson patients. Although a number rat analogues of human Parkinson's disease have been developed for evaluating the efficacy of drug therapies, it is not known whether L-dopa has a similar selective action on the motor symptoms in the rat models. To examine the effectiveness of L-dopa in reversing the motor deficits in rats, we administered 6-OHDA unilaterally to produce hemi-Parkinson rats, which were then trained to reach for food using either their impaired (contralateral to the lesion) limb or their good (ipsilateral to the lesion) limb. To assess the skill, accuracy and range of limb movement, rats reached for pasta from a horizontal array of 260 vertically orientated pieces of pasta. The number and location of pasta pieces taken from this matrix was calculated and the qualitative aspects of the reaching movements were rated. The quantitative data on pasta sticks retrieved indicated that forelimb extension and movement radius around the shoulder joint was reduced by 6-OHDA treatment and did not improve after chronic L-dopa treatment. The qualitative analysis showed that grasping patterns, paw movements and body movements impaired by the lesion were also not improved by L-dopa treatment. These findings are the first in the rat to suggest that whereas L-dopa has a general activating effect on the rat's whole-body movements, as displayed in contralateral rotation, its effectiveness does not extend to skilled forelimb movements. The results are discussed in relationship to the idea that the restoration of some skilled movements may require normal synaptic function.

Progressive Motor Cortex Functional Reorganization Following 6-Hydroxydopamine Lesioning in Rats

“…In addition, L-dopa was barely effective in modulating threshold currents (consistent with that reported in patients) (Lefaucheur, 2005) but restored the ability to evoke distal forelimb movements. The lack of effect in the rostral area is consistent with evidence that L-dopa did not improve skilled forelimb movements in hemiparkinsonian rats (Metz et al, 2001). The failure of L-dopa in normalizing all parameters remains puzzling.…”

“…The forelimb area at the ipsilateral side showed persistent decrease in size and excitability, the rostral area being more affected than the caudal one. This may explain the impairment in the skilled reaching movement in hemiparkinsonian rats (Miklyaeva et al, 1994;Whishaw et al, 1997;Metz et al, 2001), since the complex sequences of reach-to-grasp movement are represented in the rostral forelimb area (Ramanathan et al, 2006), which is homologous to the premotor/supplementary motor area of primates . Surprisingly, the size of the contralateral rostral forelimb area appeared increased after 3 d. This short-term reorganization was probably due to the preserved plasticity of the forelimb in the unlesioned hemisphere.…”

Manganese Inhalation as a Parkinson Disease Model

“…Detailed analyses of skilled limb movements, such as the reach-to-grasp movement, show very similar motor components in humans and in rodents [78, 79]. An analysis of the movements used by the rodents indicates that a reach consists of postural adjustments that result in the body being supported by the diagonal couplet of the hind limb ipsilateral to the reaching forelimb and its opposite forelimb.…”

Vocal training, levodopa, and environment effects on ultrasonic vocalizations in a rat neurotoxin model of Parkinson disease

“…For example, forced use of a limb results in behavioral sparing when exercise training is initiated before or early after the administration of a dopamine-depleting neurotoxin [31,33–35]. Chronic levodopa therapy improves some gross motor deficits such as rotational responses [36], but not skilled forelimb movements including reaching and grasping for food [37]. In rats, early exercise intervention (therapy) has been shown to protect viable dopamine neurons in the substantia nigra as well as improve behavioral sensorimotor outcomes [20,26,35,38,39].…”