Effect of 5-Hydroxytryptamine
            <sub>1</sub>
            Serotonin Receptor Agonists on Noxiously Stimulated Micturition in Cats With Chronic Spinal Cord Injury

Gu, Baojun; Thor, Karl B.; Reiter, Jerome P.; Dolber, Paul C.

doi:10.1016/j.juro.2007.01.110

Cited by 16 publications

(19 citation statements)

References 10 publications

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“…Previous urodynamic studies in anesthetized cats (17,18,29) support a supraspinal location of 5-HT 1A receptors that facilitate URS activity. This support stems from urodynamic studies that showed a robust, dose-dependent, and WAY-100635-sensitive enhancement of spontaneous URS EMG activity in chloralose-anesthetized cats under conditions of bladder irritation when the spinal cord is intact (29) but not when the spinal cord is transected, even after spinal bladder reflexes have emerged following spinal shock (17,18).…”

Section: Discussionmentioning

confidence: 91%

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats

Venkateswarlu¹,

Langdale²,

Ukai³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Urine storage is facilitated by somatic (pudendal nerve) and sympathetic [hypogastric nerve (HgN)] reflexes to the urethral rhabdosphincter (URS) and urethral smooth muscle, respectively, initiated by primary afferent fibers in the pelvic nerve (PelN). Inhibition of storage reflexes is required for normal voiding. This study characterizes a urine storage reflex inhibitory network that can be activated by PelN afferent fibers concurrently with the reflexes themselves. Electrical stimulation of PelN produced evoked potentials recorded by URS EMG electrodes (10-ms latency) or HgN electrodes (60-ms latency) in chloralose-anesthetized cats. When a second (i.e., paired) pulse of the same stimulus intensity was applied to the PelN 50-500 ms after the first, the reflexes evoked by the second stimulus were inhibited. The inhibition was maximal at paired-pulse intervals of 50-100 ms and remained after acute spinal transection at T10, confirming that the inhibitory center is located in the spinal cord. The 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tertralin (8-OH-DPAT; 3-300 mug/kg iv) consistently reduced the paired-pulse inhibition from 20% to 60% of control in spinal-intact animals but had no effect in acute spinal animals (i.e., supraspinal site of action). N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-2-pyridinylcyclohexanecarboxamide maleate (300 mug/kg iv) completely reversed 8-OH-DPAT's effects. The PelN-HgN reflex paired-pulse inhibition was not affected by 8-OH-DPAT. These results indicate the presence of a spinal, urine storage reflex, inhibitory center (SUSRIC) that is activated within 50 ms after activation of the reflexes themselves. SUSRIC is inhibited (disfacilitated) by supraspinal 5-HT(1A) receptors.

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Section: Discussionmentioning

confidence: 91%

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats

Venkateswarlu¹,

Langdale²,

Ukai³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) (33) and serotonergic receptor agonists (7,30,34) have prominent inhibitory effects on bladder overactivity in anesthetized cats, indicating a role of endogenous monoamines in the control of the bladder as well as a possible role of these neurotransmitters in the actions of tramadol on bladder reflexes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

Zhang

Mally

Ogagan

et al. 2012

American Journal of Physiology-Renal Physiology

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Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3–7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50–60% of the saline control capacity. Tramadol administered alone in low doses (0.3–1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3–7 mg/kg) increased bladder capacity (50–60%). TNS in combination with tramadol (3–7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects.

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“…For example, in the cat, activation of 5-HT 1A receptors inhibits the parasympathetic excitatory input to the urinary bladder (14,15,27,31,36). On the other hand, in the rat, activation of 5-HT 1A receptors enhances reflex activity of the bladder and sphincter (1,2,12,20), whereas block of 5-HT 1A receptors suppresses bladder and sphincter activity, suggesting that endogenous 5-HT exerts a tonic influence on the neural pathways controlling the lower urinary tract (1,9,17,19,26,32).…”

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confidence: 99%

Role of 5-HT_1A receptors in control of lower urinary tract function in anesthetized rats

Cheng

Groat

2010

American Journal of Physiology-Renal Physiology

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The role of 5-hydroxytryptamine (5-HT) 1A (5-HT1A) receptors in lower urinary tract function was examined in urethane-anesthetized female Sprague-Dawley rats. Bladder pressure and the external urethral sphincter electromyogram (EUS EMG) activity were recorded during continuous-infusion transvesical cystometrograms (TV-CMGs) to allow voiding and during transurethral-CMGs (TU-CMGs) which prevented voiding and allowed recording of isovolumetric bladder contractions. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT 1A receptor agonist, decreased volume threshold (VT) for initiating voiding and increased contraction amplitude (CA) during TU-CMGs but decreased CA during TV-CMGs. 8-OH-DPAT prolonged EUS bursting as well as the intrabursting silent periods (SP) during voiding., a 5-HT 1A antagonist, increased VT, increased residual volume, markedly decreased voiding efficiency, decreased the amplitude of micturition contractions recorded under isovolumetric conditions, and decreased the SP of EUS bursting. These results indicate that activation of 5-HT 1A receptors by endogenous 5-HT lowers the threshold for initiating reflex voiding and promotes voiding function by enhancing the duration of EUS relaxation, which should reduce urethral outlet resistance. micturition; external urethral sphincter; urinary bladder; electromyogram; serotonin THE LOCALIZATION OF NERVE terminals containing serotonin (5-hydroxytryptamine; 5-HT) in sympathetic, parasympathetic (6), and urethral sphincter motor nuclei (27) in the lumbosacral spinal cord has focused attention on the role of 5-HT as a neurotransmitter in the central neural pathways controlling lower urinary tract function (9,11,25,28). Pharmacological studies in animals have revealed that administration of 5-HT receptor agonists or antagonists modulates reflex bladder and urethral sphincter activity (1, 2, 12, 14, 15, 17, 19, 20, 30 -32, 34, 36). These effects are mediated by activation of multiple 5-HT receptors, which are distributed at various sites in the central pathways controlling the lower urinary tract (9,12,16,21,28,29,37).The effect of 5-HT on bladder and sphincter activity varies in different species. For example, in the cat, activation of 5-HT 1A receptors inhibits the parasympathetic excitatory input to the urinary bladder (14,15,27,31,36). On the other hand, in the rat, activation of 5-HT 1A receptors enhances reflex activity of the bladder and sphincter (1,2,12,20), whereas block of 5-HT 1A receptors suppresses bladder and sphincter activity, suggesting that endogenous 5-HT exerts a tonic influence on the neural pathways controlling the lower urinary tract (1,9,17,19,26,32).In rats, 5-HT 1A receptors may regulate urine storage as well as voiding by facilitating two types of external urethral sphincter (EUS) activity (1, 2, 12). Administration of a 5-HT 1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), enhances tonic EUS activity that occurs during bladder filling. This would be expected to promote urinary continence. 8-OH-DPAT also enhanc...

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Effect of 5-Hydroxytryptamine ₁ Serotonin Receptor Agonists on Noxiously Stimulated Micturition in Cats With Chronic Spinal Cord Injury

Cited by 16 publications

References 10 publications

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

Role of 5-HT_1A receptors in control of lower urinary tract function in anesthetized rats

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Effect of 5-Hydroxytryptamine 1 Serotonin Receptor Agonists on Noxiously Stimulated Micturition in Cats With Chronic Spinal Cord Injury

Cited by 16 publications

References 10 publications

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT1A receptors in female cats

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT1A receptors in female cats

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

Role of 5-HT1A receptors in control of lower urinary tract function in anesthetized rats

Contact Info

Product

Resources

About

Effect of 5-Hydroxytryptamine ₁ Serotonin Receptor Agonists on Noxiously Stimulated Micturition in Cats With Chronic Spinal Cord Injury

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats

Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats

Role of 5-HT_1A receptors in control of lower urinary tract function in anesthetized rats