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• W1566450138 abstract "The aims of this thesis were to characterise further lesion-induced impairments inunilateral rodent models of Parkinson’s disease (PD) on a more cognitive level and toinvestigate the effects of cell replacement therapies on these tests.Chapter 3.1 deals with the effects of dopamine depletion on a lateralised choicereaction time task in the Skinner box as this apparatus is more widely available thanthe 9-hole boxes on which initial studies have been based. Unilateral near completelesions of the nigro-striatal pathway induced a stable side bias that was comparableto the lesion-induced deficits that have been reported in the 9-hole box apparatus.Chapter 3.2 reports on the effects of similar lesions on a more spatial reaction timetask and the effects of engraftment of dopamine rich tissue in the denervatedstriatum. The lesions induced a spatial bias that was only marginally improved by thecell transplantation, clearly showing the limitations of ectopic graft placement.Nevertheless, small but significant improvements on that task could be shown asgrafted animals performed with higher accuracy and had reduced movement timescompared to the lesion only counterparts. Chapter 3.3 explores the lesion-induceddeficit in more detail by implementing an error correction rule on the operant task toenforce a change in the animals’ response strategy. The results of this chapterconfirmed earlier findings, that the dopamine depletion produced by the lesion givesrise to a strong near hole bias on the contralateral side which did not recover, evenwith extensive post lesion testing, i.e. the lesion-induced deficit is most likely to becaused by a misrepresentation of response space, rather than caused by a shift inresponse strategy.The second strand of this thesis focuses on the development of mouse models ofsimilar dopamine-depleting lesions that are typically used in rat models of PD. InChapter 3.4 the three most common lesion models are compared to each other onan extensive battery of simple motor tests. The aim was both to characterise thebehavioural impact of dopamine depletion in different sites, as well as to identifyappropriate hand tests, capable of distinguishing lesions greater than 70% depletion.The differences and similarities between lesions were evaluated and correlationsbetween behavioural performance and nigral cell loss were observed. In Chapter 3.5I developed parameters which allowed application of the lateral choice reaction timetask to mouse models of dopamine depletion. Here I demonstrate the effects of twolesions, either to the medial forebrain bundle or the substantia nigra, on the sametask conducted in mice. Lesioned mice of the former group displayed a strongerdeficit largely because of the larger dopamine depletion. Subsequently, in Chapter3.6 I characterise the effects of primary fetal tissue grafts on the previouslyestablished model and task. Primary fetal tissue was able to ameliorate some of thelesion-induced deficits on an operant choice reaction time task and a series of simplemotor screens.The results of both strands of research in the present thesis have implications for the understanding of the cognitive and motor deficits that are induced by the mostcommonly used lesion model of PD and for the parameters that can be recovered bycell replacement therapies. The primary fetal tissue will serve as a baseline, againstwhich future stem cell based therapies can be measured" @default.
• W1566450138 created "2016-06-24" @default.
• W1566450138 creator A5080450062 @default.
• W1566450138 date "2012-01-01" @default.
• W1566450138 modified "2023-09-24" @default.
• W1566450138 title "Behavioural analysis of 6-hydroxydopamine rodent models of Parkinson's disease" @default.
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