Conversion of the Modulatory Actions of Dopamine on Spinal Reflexes from Depression to Facilitation in D<sub>3</sub>Receptor Knock-Out Mice

Clemens, Stefan; Hochman, Shawn

doi:10.1523/jneurosci.3698-04.2004

Cited by 104 publications

(78 citation statements)

References 64 publications

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“…This was in spite of the fact that D 1 and D 2 receptor agonists reduced evoked polysynaptic potentials as predicted by previous reports (Clemens and Hochman 2004). This suggests that transmission from propriospinal relay interneurons in the sacral cord to the lumbar CPG was not affected.…”

Section: Monoaminergic Depression Of Rhythmic Activitysupporting

confidence: 85%

“…DA has been observed to cross react with ␣ 2 receptors in other parts of the brain (Cornil et al 2002), and paracrine release of DA within the dorsal horn could potentially activate neighboring synapses (Mundorf et al 2001;Ridet et al 1993). One issue is that our DA bath concentrations were high, and concentration-dependent effects on evoked reflexes have been reported in the 10-to 20-M range using a mouse spinal cord preparation (Clemens and Hochman 2004). Nevertheless, it does not detract from our observations that direct activation of DA receptors does not suppress cauda equina evoked locomotor-like activity.…”

Section: Monoaminergic Depression Of Rhythmic Activitymentioning

confidence: 98%

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Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

Gordon

Whelan²

2006

Journal of Neurophysiology

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. Monoaminergic projections are among the first supraspinal inputs to innervate spinal networks. Little is known regarding the role of monoamines in modulating ongoing locomotor patterns evoked by endogenous release of neurotransmitter. Here we activate a locomotor-like rhythm by electrical stimulation of afferents and then test the modulatory effects of monoamines on the frequency, pattern, and quality of the rhythm. Stimulation of the cauda equina induced a rhythm consisting of left-right and ipsilateral alternation indicative of locomotor-like activity. First, we examined the effects of noradrenaline (NA), serotonin (5-HT), or dopamine (DA) at dose levels that did not elicit locomotor activity. Bath application of NA and DA resulted in a depression of the cauda-equina-evoked rhythm. Conversely, bathapplied 5-HT increased both the amplitude and cycle period of the evoked rhythm, an effect that was mimicked by the addition of 5-HT 2 agonists to the bath. Application of 5-HT 7 agonists disrupted the evoked rhythmic behavior. Next, we examined the effects of NA ␣ 1 and ␣ 2 agonists and found that the suppressive effects of NA on the rhythm could be reproduced by adding the ␣ 2 agonist, clonidine, to the bath. In contrast, bath applying the ␣ 1 agonist, phenylephrine, increased the amplitude and duration of the cycle period. Finally, the suppressive effects of DA were not replicated by the administration of D 1 , D 2 , or D 3 agonists although application of NA ␣ 2 antagonists reversed the effects of DA. Application of D 1 agonists, increased the amplitude of the bursts but did not affect the cycle period. Our results indicate that monoamines can control the expression, pattern, and timing of cauda-equina-evoked locomotor patterns in developing mice.

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Section: Monoaminergic Depression Of Rhythmic Activitysupporting

confidence: 85%

Section: Monoaminergic Depression Of Rhythmic Activitymentioning

confidence: 98%

Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

Gordon

Whelan²

2006

Journal of Neurophysiology

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“…Moreover, the disinhibition of IML leads to an increase in sympathetic output that might explain the alteration of ANS observed by some authors [11,29]. In addition, there is wide evidence that the dopaminergic system dysfunction induces hypertension [30][31][32], as supported by experimental studies in dopamine D3 knockout mice that has been proposed as a potential animal model for RLS [33].…”

Section: Tablementioning

confidence: 97%

Is autonomic nervous system involved in restless legs syndrome during wakefulness?

et al. 2014

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A B S T R A C TObjective: To investigate cardiovascular autonomic function in patients with restless leg syndrome (RLS) by means of cardiovascular reflexes and heart rate variability (HRV) during wakefulness. Methods: Twelve RLS patients and 14 controls underwent cardiovascular function tests including headup tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip, and cold face. HRV analysis was performed in the frequency domain using both autoregressive (AR) and fast Fourier transform algorithms in rest supine condition and during HUTT.Results: There was a significant increase in systolic blood pressure values in supine rest condition and a trend toward a lower Valsalva ratio in RLS patients with respect to controls. The significant and physiological changes of HRV at HUTT detected in healthy subjects were not found in RLS patients. Conclusion: RLS patients exhibit a tendency toward hypertension, reduced amplitude of both sympathetic and parasympathetic responses at HUTT, as well as blunted parasympathetic drive to blood pressure changes. These findings, if confirmed by more controlled studies, might support the hypothesis of autonomic nervous system involvement during wakefulness and consequently an enhanced cardiovascular risk in RLS.

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“…Clemens et al (2006) suggested a decreased D3R-mediated inhibition of spinal sensory and reflex circuits as a pathogenetic concept in RLS (Clemens et al, 2006). This is supported by the switch from inhibitory to excitatory dopamine effects on spinal reflexes in D3RϪ/Ϫ mice (Clemens and Hochman, 2004) that resembles the increased excitability of the flexor reflex detected in RLS patients (Bara-Jimenez et al, 2000). Additionally, the most commonly and successfully used dopamine agonists have a relevant if not predominant D 3 agonism.…”

Section: Introductionmentioning

confidence: 97%

Dopamine D₃Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice

Dowling¹,

Klinker²,

Stadelmann³

et al. 2011

J. Neurosci.

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Restless legs syndrome (RLS) is a common neurological disorder whose exact pathophysiological mechanism remains unclear despite the successful use of dopaminergic treatment and recent discovery of predisposing genetic factors. As iron deficiency has been associated with RLS for some patients and there is evidence for decreased spinal dopamine D 3 -receptor (D3R) signaling in RLS, we aimed at establishing whether D3R activity and iron deficiency share common pathways within the pathophysiology of RLS sensory and motor symptoms.Using a combined mouse model of iron deficiency and dopamine D 3 -receptor deficiency (D3RϪ/Ϫ), circadian motor symptoms were evaluated by continuous recording of spontaneous wheel running activity. Testing the acute and persistent pain responses with the hot-plate test and formalin test, respectively, assessed sensory symptoms.A 15 week iron-deficient (ID) diet alone increased acute and persistent pain responses as compared to control diet. As compared to C57BL/6 (WT), homozygous D3RϪ/Ϫ mice already exhibited elevated responses to acute and persistent pain stimuli, where the latter was further elevated by concurrent iron deficiency. ID changed the circadian activity pattern toward an increased running wheel usage before the resting period, which resembled the RLS symptom of restlessness before sleep. Interestingly, D3RϪ/Ϫ shifted this effect of iron deficiency to a time point 3-4 h earlier.The results confirm the ability of iron deficiency and D3RϪ/Ϫ to evoke sensory and motor symptoms in mice resembling those observed in RLS patients. Furthermore this study suggests an increase of ID-related sensory symptoms and modification of ID-related motor symptoms by D3RϪ/Ϫ.

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Conversion of the Modulatory Actions of Dopamine on Spinal Reflexes from Depression to Facilitation in D₃Receptor Knock-Out Mice

Cited by 104 publications

References 64 publications

Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

Is autonomic nervous system involved in restless legs syndrome during wakefulness?

Dopamine D₃Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice

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Conversion of the Modulatory Actions of Dopamine on Spinal Reflexes from Depression to Facilitation in D3Receptor Knock-Out Mice

Cited by 104 publications

References 64 publications

Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

Monoaminergic Control of Cauda-Equina-Evoked Locomotion in the Neonatal Mouse Spinal Cord

Is autonomic nervous system involved in restless legs syndrome during wakefulness?

Dopamine D3Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice

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Product

Resources

About

Conversion of the Modulatory Actions of Dopamine on Spinal Reflexes from Depression to Facilitation in D₃Receptor Knock-Out Mice

Dopamine D₃Receptor Specifically Modulates Motor and Sensory Symptoms in Iron-Deficient Mice