期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 27, 期 12, 页码 3216-3225出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1460-9568.2008.06276.x
关键词
6-hydroxydopamine; dopamine; GABA; micturition reflex; periaqueductal gray
The periaqueductal gray (PAG) is critically involved in the micturition reflex, but little is known about the neuronal mechanisms involved. The present study elucidated dynamic changes in dopamine (DA), glutamate and gamma-aminobutyric acid (GABA) in the rat PAG during the micturition reflex, with a focus on dopaminergic modulation using in vivo microdialysis combined with cystometrography. Extracellular levels of DA and glutamate increased, whereas levels of GABA decreased, in parallel with the micturition reflex. Application of a D-1 receptor antagonist into the PAG produced increases in maximal voiding pressure (MVP) and decreases in intercontraction interval (ICI), suggesting that the micturition reflex was facilitated by D-1 receptor blockade. The D-1 receptor antagonist prevented micturition-induced decreases in GABA efflux but had no effect on DA or glutamate. Neither a D-2 receptor antagonist nor a D-1/D-2 receptor agonist affected these neurochemical and physiological parameters. Micturition-induced inhibition of GABA was not observed in 6-hydroxydopamine (6-OHDA)-lesioned rats, an animal model of Parkinson's disease. 6-OHDA-lesioned rats exhibited bladder hyperactivity evaluated by increases in MVP and decreases in ICI, mimicking facilitation of the micturition reflex induced by D-1 receptor blockade. These findings suggest that the micturition reflex is under tonic dopaminergic regulation through D-1 receptors, in which a GABAergic mechanism is involved. Bladder hyperactivity observed in 6-OHDA-lesioned rats may be caused by dysfunction of GABAergic regulation underlying the micturition reflex. The present findings contribute to our understanding not only of the neurophysiology of the micturition reflex but also of the pathophysiology of lower urinary tract dysfunction in patients with Parkinson's disease.
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