Disordered Locomotion in the AWAGU Mutant Rat and the Effects of L-dopa or Fetal Midbrain Grafts

CATHERINE TSANG, Anthony P Payne, Roger Sutcliffe, Jacqueline M Campbell, Glenda Favor, David Russell, Neil K Bennett, Debbie J Clarke, Richard Branton, Wayne Davies, Elaine Simpson, Ronald Baxendale

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The AS/AGU rat arose as a spontaneous mutation within a closed inbred colony of Albino Swiss (AS) rats. The mutation is recessive' and AS/AGU rats have now
been isolated as a true breeding substrain. The AS/AGU mutant is characterized by serious movement impairments which particularly affect the hind limbs causing rigidity, a staggering gait, and a tendency for the hind quarters to fall over every few steps.2 The first signs can be detected 15-35 days after birth through a combination of clumsy gait, high stepping, tail elevation, and a slight
whole-body tremor. In older rats, the fully developed condition includes difficulty in initiating movement. There are no obvious gross morphologic differences between the brains of normal and mutant AS/AGU rats: neocortical and cerebellar histology appears normal. Immunocytochemical studies have revealed deficits in monoaminergic systems, including dopaminergic cell
groups related to mesostriatal pathways,' serotonergic cells of the dorsal ra~he,~ andnoradrenergic cells of the locus coerule~s.~ There is significant depletion of glucose use in the substantia nigra pars compacta, subthalamic nucleus, and ventrolateral thalamus.' Compared with AS rats, there is a 30% reduction in dopamine levels in the dorsal and lateral caudate-putamen of adult AS/AGU rats as measured by postmortem striatal micropunch and high-performance liquid chromatography with electrochemical detection (HPLC-ECD). la6 However, a greater reduction is found in extracellular levels of dopamine as measured by in vivo microdialysis of conscious animals/HPLC-ECD; here dopamine levels in the mutant are down to only 10-20% of control values (J.M. Campbell, unpublished data)
Original languageEnglish
Pages (from-to)832-834
JournalMovement Disorders
Issue number5
Publication statusPublished - 12 Feb 1998


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