Attentional dysfunction in Parkinson’s disease : the role of central amygdala dopamine and possible treatment options
MetadataShow full item record
While it is known that Parkinson’s disease (PD) results in motor dysfunction, there exist many cognitive symptoms including impairments in attention. PD patients demonstrate impaired ability to switch attention between tasks, rules, or stimuli, ignore irrelevant stimuli, and sustain attention to stimuli or tasks. Dysfunction of the mesocortical system is suggested to be responsible for these attentional deficits. However, attentional impairments surface in the early stages of the disease and cortical areas are among the last regions to show pathology. Further, it is not well understood how effective common dopamine replacement therapy (L-dopa) is in restoring attentional dysfunction. Recent work suggests that L-dopa may only improve some aspects of attentional function in PD, thus making further examination of the effects of L-dopa on attentional function important. And as L-dopa also has many other limitations (e.g. possible development of unwanted motor side effects), it is also necessary to investigate other possible treatments for these dysfunctions. In this dissertation, I first examined the role of dopaminergic function in the central amygdala (CeA) in the regulation of attentional processes in rodents. I found that dopaminergic input into the CeA mediated by D1 receptors is necessary for attention switching (i.e. disengagement behavior) and selective and sustained attention in rodents. Then I investigated the effects of L-dopa on these two different types of attentional deficits in a rodent model of PD in which dopamine is depleted unilaterally using the neurotoxin, 6-hydroxydopamine. While L-dopa was able to recover basic attentional switching, more complex attentional processes (i.e. selective and sustained attention) were not recovered. In an attempt to find a better treatment for these deficits, I used methylene blue (MB), a metabolic enhancer and antioxidant, to target mitochondrial dysfunction, a characteristic of all compromised dopamine cells. While MB was able to provide moderate neuroprotection in this model of PD, it was unable to recover attentional function. Taken together, my dissertation work demonstrates that attentional function is partly regulated by sub-cortical CeA dopamine mechanisms and that PD-related attentional dysfunction may require a multi-faceted treatment approach.