d-Amphetamine enhances skilled reaching after ischemic cortical lesions in rats
DeAnna L. Adkins, Theresa A. Jones∗
Psychology Department and Neuroscience Institute, University of Texas at Austin, 1 University Station, A8000, Austin, TX 78746, USA Received 24 November 2004; received in revised form 13 January 2005; accepted 13 January 2005
AbstractUnilateral sensorimotor cortical (SMC) lesions in rats impair reaching and grasping movements of the contralateral forelimb. These impairments can be improved using motor rehabilitative training on a skilled reaching task, but the training may be far from sufﬁcient to return animals to pre-lesion levels of performance. Because d-amphetamine (AMPH) has been found to promote neuroplastic responsesto injury and to be very beneﬁcial when combined with some (but not all) types of rehabilitative training, we asked in this experiment whether it could improve the efﬁcacy of rehabilitative training in skilled reaching. Ten to 14 days after unilateral ischemic (endothelin-1 induced) lesions of the SMC, adult rats were given a 3-week regimen of AMPH (1 mg/kg) coupled with daily rehabilitativetraining on a skilled reaching task, the single pellet retrieval task. AMPH treatment not only dramatically improved reaching performance compared with saline-injected controls, the AMPH treated rats surpassed pre-lesion levels of performance by the end of the rehabilitative training period. The greater performance in AMPH compared to saline-treated rats was still evident at 1 month, but not at 2 and 3months, after the end of rehabilitative training. Thus, AMPH treatment can greatly enhance the efﬁcacy of rehabilitative training on a skilled reaching task after unilateral SMC lesions, but alternate injection and training regimes may be needed to produce permanent improvements. © 2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Motor rehabilitation; Catecholamines; Single pelletretrieval task; Endothelin-1
Motor rehabilitative training after brain injury enhances motor recovery and neural plastic changes in affected brain regions [23,28]. Complex “acrobatic” motor skills training after unilateral sensorimotor cortex (SMC) lesions enhances synaptic structural plasticity in the cortex opposite the lesion and reduces tissue loss in peri-lesion cortex of rats [6,21]. In intactrats, training on a skilled forelimb reaching task increases motor cortical dendrites [5,41] and synapses per neuron  contralateral to the trained limb. In rats  and monkeys [3,29] reach training of the impaired forelimb also spares the loss of distal forelimb motor representation areas adjacent to ischemic infarcts, as assessed with microstimulation mapping. The combination of reachtraining and exposure to a complex environment after unilateral middle cerebral artery occlusions in rats has been found to improve reaching ability and to enhance dendritic growth in the cortex opposite the lesion . However, motor rehabilitative training alone may
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not besufﬁcient to return animals to pre-lesion levels of performance and a greater efﬁcacy of reach training is likely to be achieved by combining it with other therapies [2,20]. AMPH administration has been found to promote improved behavioral function [7,9–17,19,25,26,32–35,37–39], as well as neurotrophic and neuroplastic responses [27,33] following brain damage. In several animal studies, amphetamine hasbeen found to improve performance when combined with training on beam-walking tasks, which are sensitive to impairments in postural support and coordinated limb use in locomotion [13,14,16]. AMPH also improves visual impairments in cats  and forelimb placing behavior in rats  with cortical damage. In some (but not all) human studies, AMPH has been found to improve motor function [7,38]...