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Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions
Authors:Stephen B. Dunnett   Ian Q. Whishaw   Derek C. Rogers  Graham H. Jones
Affiliation:1. IRCCS Fondazione Santa Lucia, Rome, Italy;2. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy;3. Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden;4. School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Italy;5. Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy
Abstract:
The capacity of dopamine (DA)-rich embryonic grafts to influence performance in a skilled motor task has been assessed. In two separate experiments, unilateral 6-hydroxydopamine lesions of forebrain DA systems induced a neglect of the contralateral limb and an almost total preference for use of the ipsilateral limb when reaching through the bars of a cage for food pellets. If the food paw was restrained, either by a bracelet or by injection of a local anaesthetic, the lesioned rats would continue to make many reaching attempts with the contralateral paw, but on the great majority of these attempts they were unsuccessful in grasping or retrieving food. DA-rich grafts, reinnervating the denervated caudate-putamen, provided no detectable benefit to the lesioned rats, neither in reducing the ipsilateral bias in their side preference, nor in increasing their success when constrained to reaching with the contralateral limb. This failure to benefit from the grafts is not due to the grafts themselves not being viable, since the same rats showed substantial compensation of whole body motor asymmetries in spontaneous and drug-induced rotation, and a reduction of asymmetry in a battery of neurological tests of sensorimotor function. The results are discussed in terms of the degree of anatomical integration of the grafts into the host neural circuitry, and the neural organization necessary for the performance of different classes of behavior.
Keywords:Dopamine   6-Hydroxydopamine   Transplant   Limb use   Paw use   Rotation
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