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Subthalamic nucleus lesions induce deficits as well as benefits in the hemiparkinsonian rat

Authors

  • Jasmine M. Henderson,

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    • *

      Present address: Prince of Wales Medical Research Institute, High St., Randwick, NSW 2031, Australia

  • Lucy E. Annett,

    1. MRC Cambridge Centre for Brain Repair and Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
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  • Lawrence J. Ryan,

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    • Present address: Department of Psychology, Oregon State University, Moreland Hall, Corvallis, OR 97331-5303, USA

  • Wesley Chiang,

    1. MRC Cambridge Centre for Brain Repair and Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
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  • Seiko Hidaka,

    1. MRC Cambridge Centre for Brain Repair and Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
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  • Eduardo M. Torres,

    1. MRC Cambridge Centre for Brain Repair and Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
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  • Stephen B. Dunnett

    1. MRC Cambridge Centre for Brain Repair and Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
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: Dr L. E. Annett, as above. E-mail: la100@cus.cam.ac.uk

Abstract

Lesions of the subthalamic nucleus can restore some imbalances in motor output of the basal ganglia induced by nigrostriatal dopamine depletion, and have been proposed as a potential therapy for Parkinson's disease. Although there is substantial supporting evidence from experimental studies in both rats and primates, there is less information on the effects of subthalamic lesions alone. In order to characterize potential side effects, the present study evaluates the behavioural effects of unilateral excitotoxic lesions of the subthalamic nucleus in rats that have previously received either unilateral saline or 6-hydroxydopamine injections into the nigrostriatal bundle on the same side. The 6-hydroxydopamine lesions induced ipsilateral orientation asymmetries in head position and body axis bias, rotational asymmetries following injections of direct or indirect dopamine agonists, neglect of contralateral stimuli, and a reduction in the numbers of pellets retrieved with the contralateral paw in a skilled reaching task. Subsequent excitotoxic lesions of the subthalamic nucleus reduced (but did not abolish) rotational asymmetries, had no effects on the measures of neglect and skilled paw-reaching, and produced contralateral orientation biases in head turning and body axis curling. Rats that received subthalamic lesions alone exhibited de novo impairments comprising contralateral biases in the orientation tests. These results support a neuromodulatory role of the subthalamic nucleus in regulating motor outputs of the basal ganglia, and caution that there may be distinct side effects of the lesion by itself. Whereas some impairments attributable to dopamine depletion may be alleviated by subthalamic manipulations, other symptoms are not, or may even be aggravated.

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