Lesions of the nigrostriatal dopamine system in rats produce a syndrome of aphasia, adipsia, bradyknesia, and profound sensorimotor neglect, symptoms similar to those seen in Parkinson's Disease. In the hemi-Parkinsonian rat, stimulation with drugs that induce dopamine release (e.g., amphetamine) or act as agonists at dopamine receptor (e.g., apomorphine) induce behavioral asymmetries, and in particular rotational behavior. Substantia nigra anlage or adrenal medulla tissue grafted into or adjacent to the dopamine-denervated striatum have been shown to alleviate many of the behavioral deficits associated with unilateral nigrostriatal dopamine denervation. Experiments are proposed using behavioral, neurochemical, and morphological methods to further delineate the mechanisms mediating recovery of function after grafts of adrenal medulla or substantia nigra anlage. Our results suggest that these types of grafts produce their effects on the dopamine-denervated striatum by different mechanisms, that multiple mechanisms are involved, and that the mechanism(s) may vary with the type of cell that is transplanted into the brain. For example, if animals with adrenal medulla grafts are tested for rotational behavior with both amphetamine and apomorphine some animals have decreased amphetamine-induced turning and others have decreased apomorphineinduced turning, fewer than 10% have both. With grafts of substantia nigra anlage individual differences in behavior are seen in the response to amphetamine. Some animals with these grafts exhibit less amphetamine-induced turning, others reverse their direction of turning. The relationship between behavioral recovery and neurochemical indices of neurological function following these grafts is the topic of the research proposed here. Defining the events necessary for behavioral recovery after these grafts will illuminate ways in which to improve their survival and behavioral efficacy. By studying individual differences in graft effects, rather than studying only group effects, those mechanisms and procedures most likely to promote recovery of function in all individuals can be discerned. In the experiments proposed we take the next step towards defining the neurochemical processes mediating individual differences in behavioral recovery after transplantation of dopaminergic tissue into brain. The neural processes mediating recovery of function in this animal model of Parkinson's Disease are not necessarily unique. Thus, the results of these experiments may also contribute to the development of improved therapies for other neurological disorders, including Alzheimer's Disease and Huntington's Disease.
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