Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: Long-term behavioral, biochemical, and histochemical studies

Authors

  • William J. Freed PhD,

    Corresponding author
    1. Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC
    2. The Department of Histology, Karolinska Institute, Stockholm, Sweden
    3. The Department of Pharmacology, University of Colorado School of Medicine, Denver, CO
    • NIMH, Division of Special Mental Health Research, St. Elizabeths Hospital, WAW Bldg, Washington, DC 20C32
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  • Mark J. Perlow MD,

    1. Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC
    2. The Department of Histology, Karolinska Institute, Stockholm, Sweden
    3. The Department of Pharmacology, University of Colorado School of Medicine, Denver, CO
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  • Farouk Karoum PhD,

    1. Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC
    2. The Department of Histology, Karolinska Institute, Stockholm, Sweden
    3. The Department of Pharmacology, University of Colorado School of Medicine, Denver, CO
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  • Ake Seiger PhD,

    1. Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC
    2. The Department of Histology, Karolinska Institute, Stockholm, Sweden
    3. The Department of Pharmacology, University of Colorado School of Medicine, Denver, CO
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  • Lars Olson PhD,

    1. Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC
    2. The Department of Histology, Karolinska Institute, Stockholm, Sweden
    3. The Department of Pharmacology, University of Colorado School of Medicine, Denver, CO
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  • Barry J. Hoffer MD,

    1. Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC
    2. The Department of Histology, Karolinska Institute, Stockholm, Sweden
    3. The Department of Pharmacology, University of Colorado School of Medicine, Denver, CO
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  • Richard Jed Wyatt MD

    1. Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC
    2. The Department of Histology, Karolinska Institute, Stockholm, Sweden
    3. The Department of Pharmacology, University of Colorado School of Medicine, Denver, CO
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Abstract

Motor deficits produced in rats by unilateral substantia nigra lesions have been found to be reduced by grafts of fetal rat substantia nigra to the dopamine-denervated caudate nucleus. In the present study these grafts were examined behaviorally, histochemically, and biochemically over six- to 10-month periods. The grafts were found to survive in a healthy condition and contain catecholaminergic cells and fibers after eight to ten months. Concentrations of dopamine in adjoining parts of the caudate nucleus were increased when examined six months after grafting. Apomorphine-induced rotation was reduced by the grafts, and these reductions persisted for at least six months. Although signs of aging were observed in the brains of the host animals when sacrificed eight to ten months after grafting, the grafts remained healthy and showed no signs of aging or deterioration. It is concluded that substantia nigra grafts can become permanent, functional constituents of the brains of host animals with prior substantia nigra lesions.

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