Lesion of the nigrostriatal dopamine system in rats produce a syndrome of aphasia, adipsia, bradykinesia, and profound sensorimotor neglect, symptoms similar to those seen if Parkinson's Disease. Grafts of dopamine-rich tissue in or near the striatum have been reported to alleviate many of the behavioral deficits produced by the destruction of nigrostriatal dopamine neurons. Experiments will investigate the neurochemical processes associated with behavioral recovery of function induced by grafts of adrenal medulla or fetal substantia nigra tissue in animals with nigrostriatal dopamine depletions. It is hypothesized that dopamine released from adrenal medulla grafts gins assess to the adjacent striatum via a compromised blood-brain-barrier to mediate the behavioral effects of these grafts. In contrast grafts of fetal tissue are thought to induce behavioral recovery by the formation of synaptic contacts. Experiments are proposed to test these hypotheses. with microdialysis in freely moving rats, experiments with adrenal medulla grafts will examine whether the blood-brain-barrier to dopamine is compromised and if so. whether this is correlated with the behavioral and neurochemical efficacy of these grafts. Experiments will then attempt to dissociate dopamine release them graft vs host of prier to determine whether there are changes in the activity of host dopaminergicneurons (e.g. neurochemical corelates of sprouting). In animals with bilateral dopamine depletion. The effect of unilateral adrenal medulla grafts on bilateral recovery of behavioral and neurochemical function will be tested. Finally, we will examine whether changes in host cholinergic activity is associated with behavioral recovery in animals with adrenal medulla grafts. The behavioral and neurochemical effects of fetal nigra grafts will be investigated using microdialysis to study the relations between graft-associated recovery of function and changes in the neurochemical function of grafted and host neurons. The relations between dopamine and acetylcholine in the straitum of animals with fetal nignal grafts amy reveal the extent of functional synaptic innervation by fetal nignal graft that occurs. Since it s well known that there is a delicate balance between dopamine and aceryicholine in the striatum, these relations may be of fundamental importance for behavioral recovery of function. Grafts of both adrenal medulla and fetal nigra tissue have already been applied clinically for the treatment of patients with severe Parkinson's Disease. The reports of the success of these grafts remains mixed. Answers about the neural mechanisms that mediate behavioral recovery of functions in animals with adrenal medulla and fetal grafts may be of fundamental importance for improving graft efficacy. The experiments proposed are a first step towards achieving this goal.
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