Midbrain control of micturition in the rat

Stone, Ella (2013). Midbrain control of micturition in the rat. University of Birmingham. Ph.D.

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The role of the periaqueductal grey (PAG) in the central control of micturition was investigated in urethane-anaesthetised rats, with the aims of furthering understanding of the central control of micturition and identifying novel therapeutic targets for urinary incontinence. Experiments using microinjection of GABAA agonists and antagonists into the midbrain showed that transmission through a localised region of the caudal ventrolateral PAG (cvlatPAG) is critical for reflex voiding and the micturition pathway is normally subject to tonic inhibitory GABAergic control. Experiments to determine the role of dopamine in controlling micturition by selectively lesioning dopamine-containing neurons in the cvlatPAG and microinjection of dopamine agonists and antagonists were inconclusive and require further work. Micturition could however be suppressed completely by trains of electrical stimulation applied throughout the midbrain. Microinjection of an excitatory amino acid over the same area reduced the frequency of micturition without disrupting the pattern of voiding. Though further work is required to determine the mechanism by which electrical stimulation inhibits reflex micturition, collaboration with clinical colleagues has indicated the exciting translational potential of electrical stimulation of the midbrain in human patients to treat urinary disturbances that have proven refractory to pharmacotherapy.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine
Funders: Biotechnology and Biological Sciences Research Council
Subjects: R Medicine > R Medicine (General)
URI: http://etheses.bham.ac.uk/id/eprint/3910


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