The effects of age and L-DOPA replacement on locomotor deficits in the AS/AGU mutant rat

Russell, David (2001) The effects of age and L-DOPA replacement on locomotor deficits in the AS/AGU mutant rat. MSc(R) thesis, University of Glasgow.

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Abstract

The AS/AGU mutant rat was derived from Albino Swiss (AS) parent stock and is characterised by an ungainly staggering gait, hindlimb rigidity, whole body tremor and difficulty in initiating movement. It is highly deficient in extracellular dopamine in the dorsal caudate-putamen. It is important to know which aspects of locomotor performance show progressive deficits and which ones are responsive to L-DOPA replacement. Initially, locomotor tests were video-recorded and used to assess an age series of both AS/AGU (mutant) and AS (parent strain) rats between 20 days and 1 year. Progressive deficits with age (with initial success c. 80-90% declining to nil at one year) were found in the performance of simple tasks such as mid-air righting (being dropped upside down from 50cm and successfully turning) and walking down a series of inclined ramps of increasing width and not falling off. In infra-red monitoring, mutant rats actually showed more movement than controls a) in an acute test of 12 minutes and b) in extended tests of 22 hours. Secondly, images taken from a footfall chamber were studied using a Kontron image analysis system to determine paw contact patterns. In AS rats, whilst contact progresses forwards it is centred around the midline of the foot throughout. Conversely, mutant rats exhibited frequent footfalls in which contact was eccentric (either medial or lateral). There appeared to be most contact on the medial side of the foot than on the lateral side, confirming the staggering gait nature of the AS/AGU rat. This is indicative of the animals inability to balance as well as its failure to sustain purposeful movement. The several elements of the movement disorder are brought back into the wild-type range by treatment with L-DOPA administration (25 mg/kg/day ip + benserazide 2.5mg/kg/day ip) for 4 weeks. This drug is the standard treatment for human Parkinson's Disease. L-DOPA ameliorated mid-air righting, and performance on certain inclined ramps in AS/AGU rats. Most striking was the improvement in locomotor performance on a 5 cm ramp after week 3 of treament. The width of this ramp corresponded to the AS/AGU rat's natural gait width. The improvement of AS/AGU rats in both of these simple locomotor tasks, continued to improve over the course of the study. These results indicate that the progressive nature of the AS/AGU movement disorder and its amelioration after L-DOPA treament, would suggest that this rat could prove to be invaluable to the study of basal ganglia related disorders. It is therefore suggested that this naturally occurring mutant model could have many advantages over existing animal models, such as those with 6-OHDA and MPTP lesions.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: Tony Payne
Keywords: Neurosciences
Date of Award: 2001
Depositing User: Enlighten Team
Unique ID: glathesis:2001-72158
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 24 May 2019 15:11
Last Modified: 24 May 2019 15:11
URI: http://theses.gla.ac.uk/id/eprint/72158

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