Effects of Uptake 2 inhibition on Levodopa-induced movements in the hemiparkinsonian rat model

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dc.contributor.advisor Lipski, J en
dc.contributor.advisor Freestone, P en
dc.contributor.author Cheung, Pang Ying en
dc.date.accessioned 2017-07-25T23:13:38Z en
dc.date.issued 2016 en
dc.identifier.uri http://hdl.handle.net/2292/34499 en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Fifty years since its introduction, L-DOPA (Levodopa) remains the ‗gold-standard‘ for the treatment of Parkinson‘s disease (PD). This drug replenishes the neurotransmitter dopamine that is largely lost in the course of the disease. However, after prolonged use of the drug, patients develop motor complications such as the ‗wearing-off‘ effect and dyskinesia. To prevent or minimise these complications, strategies that aim at prolonging the half-life of L-DOPA and smoothing out the fluctuating dopamine concentrations are needed. One way to achieve this goal is to inhibit the activity of monoamine transporters that remove L-DOPA-derived dopamine from the extracellular space. Uptake 2 is a low affinity, high capacity transporter that supports the high affinity, low capacity Uptake 1 monoamine transporters (including dopamine transporters, DAT). The aim of this study was to investigate the effects of inhibiting Uptake 2 by decynium-22 (D-22) on L-DOPA-induced rotations in hemiparkinsonian rats, using the automated video-tracking system, EthoVision XT. Microinjections of the neurotoxin that damages the nigrostriatal pathway were performed with the NeuroStar stereotaxic robotic system. This system was first optimised so that the injected toxin could reach to desired brain targets. The hemiparkinsonian model was created by a unilateral injection of 6-OHDA (10 μg in 3 μL) into the medial forebrain bundle, a brainstem structure consisting of axons from the Substantia Nigra pars compacta projecting to the striatum. Using this model, apomorphine-induced rotation tests were first conducted to indirectly assess the extent of the lesion. In some animals, the extent of the lesion was also verified by analysing the loss of tyrosine hydroxylase immunoreactivity in the lesioned striatum. Rats were given 20 mg/kg (i.p.) L-DOPA alone or together with 0.1 or 1 mg/kg D-22 (i.p.). Neither of the D-22 doses potentiated L-DOPA-induced rotations during the 2 hour testing period. However, animals that were given the higher D-22 dose had a tendency to rotate more during the first 30 min after drug administration. Further studies are needed to investigate the potential of D-22 and other Uptake 2 inhibitors in potentiating L-DOPA-induced rotation and other movements in animal models of PD. If successful, these studies could lead to improved L-DOPA therapy in PD patients. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.relation.isreferencedby UoAhttp://hdl.handle.net/2292/34499 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ en
dc.title Effects of Uptake 2 inhibition on Levodopa-induced movements in the hemiparkinsonian rat model en
dc.type Thesis en
thesis.degree.discipline Biomedical Science en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 639985 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Physiology Division en
pubs.record-created-at-source-date 2017-07-26 en

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