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Journal article
Deciphering Spinal Endogenous Dopaminergic Mechanisms That Modulate Micturition Reflexes in Rats with Spinal Cord Injury
eNeuro, v 8(4), pENEURO.0157-21.2021
01 Jul 2021
PMID: 34244339
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Spinal neuronal mechanisms regulate recovered involuntary micturition after spinal cord injury (SCI). It was recently discovered that dopamine (DA) is synthesized in the rat injured spinal cord and is involved in lower urinary tract (LUT) activity. To fully understand the role of spinal DAergic machinery in micturition, we examined urodynamic responses in female rats during pharmacological modulation of the DA pathway. Three to four weeks after complete thoracic SCI, the DA precursor L-DOPA administered intravenously during bladder cystometrogram (CMG) and external urethral sphincter (EUS) electromyography (EMG) reduced bladder overactivity and increased the duration of EUS bursting, leading to remarkably improved voiding efficiency. Apomorphine (APO), a non-selective DA receptor (DR) agonist, or quinpirole, a selective DR2 agonist, induced similar responses, whereas a specific DR2 antagonist remoxipride alone had only minimal effects. Meanwhile, administration of SCH 23390, a DR1 antagonist, reduced voiding efficiency by increasing tonic EUS activity and shortening the EUS bursting period. Unexpectedly, SKF 38393, a selective DR1 agonist, increased EUS tonic activity, implying a complicated role of DR1 in LUT function. In metabolic cage assays, subcutaneous administration of quinpirole decreased spontaneous voiding frequency and increased voiding volume; L-DOPA and APO were inactive possibly because of slow entry into the CNS. Collectively, tonically active DR1 in SCI rats inhibit urine storage and enhance voiding by differentially modulating EUS tonic and bursting patterns, respectively, while pharmacologic activation of DR2, which are normally silent, improves voiding by enhancing EUS bursting. Thus, enhancing DA signaling achieves better detrusor-sphincter coordination to facilitate micturition function in SCI rats.
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Details
- Title
- Deciphering Spinal Endogenous Dopaminergic Mechanisms That Modulate Micturition Reflexes in Rats with Spinal Cord Injury
- Creators
- Shaoping Hou - Drexel UniversityJaclyn H. DeFinis - Drexel UniversityStephanie L. Daugherty - University of PittsburghChuanxi Tang - Drexel UniversityJeremy Weinberger - Drexel UniversityWilliam C. de Groat - University of Pittsburgh
- Publication Details
- eNeuro, v 8(4), pENEURO.0157-21.2021
- Publisher
- Soc Neuroscience
- Number of pages
- 20
- Grant note
- F31DK123840-01; PO1DK093424 / National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01NS099076 / National Institutes of Health National Institute of Neurological Disorders and Stroke Grant
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000728395700002
- Scopus ID
- 2-s2.0-85111354357
- Other Identifier
- 991019167902704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences