L-DOPA and quipazine elicit air-stepping in neonatal rats with spinal cord transections.

McEwen, Melanie L.; Hartesveldt, Carol Van; Stehouwer, Donald J.

doi:10.1037/0735-7044.111.4.825

Cited by 47 publications

(61 citation statements)

References 41 publications

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“…However, spinal transections eliminate all input from the brain, and it is possible that noncatecholaminergic pathways from the brainstem are necessary to support the action of L-DOPA on the spinal cord. In support of this notion, we have shown that L-DOPA, when administered in conjunction with the serotonergic agonist quipazine, elicits hindlimb stepping in 5-day-old spinally transected rats that is nearly normal in rate and amplitude (McEwen, Van Hartesveldt, & Stehouwer, 1997a). Those results suggest that the spinal cord actions of L-DOPA are necessary for eliciting locomotor activity, and demonstrate that L-DOPA activity at brainstem sites is not essential.…”

Section: Discussionmentioning

confidence: 56%

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats

Stehouwer

Hartesveldt

2000

Dev. Psychobiol.

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Section: Discussionmentioning

confidence: 56%

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats

Stehouwer

Hartesveldt

2000

Dev. Psychobiol.

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“…The rhythmic locomotor-like activity recorded in vitro displayed a stereotyped diagonal coordination pattern that corresponded to the predominantly walking-like gait observed in vivo during both olfactory guided air stepping (Fig. 1 A) (Jamon and Clarac, 1998) and free swimming (Bekoff and Trainer, 1979) as well as following pharmacological induction by the intraperitoneal injection of L-DOPA (McEwen et al, 1997). In this way, flexor and extensor synergies occurred between homolateral cervical and lumbar motor bursts, which also fired in strict left-right alternation.…”

Section: Fictive Quadrupedal Walkingmentioning

confidence: 99%

Propriospinal Circuitry Underlying Interlimb Coordination in Mammalian Quadrupedal Locomotion

Juvin¹,

Simmers²,

Morin³

2005

J. Neurosci.

199

174

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Soon after birth, freely moving quadrupeds can express locomotor activity with coordinated forelimb and hindlimb movements. To investigate the neural mechanisms underlying this coordination, we used an isolated spinal cord preparation from neonatal rats. Under bath-applied 5-HT, N-methyl-D,L-aspartate (NMA), and dopamine (DA), the isolated cord generates fictive locomotion in which homolateral cervicolumbar extensor motor bursts occur in phase opposition, as does bursting in homologous (left-right) extensor motoneurons. This coordination corresponded to a walking gait monitored with EMG recordings in the freely behaving animal. Functional decoupling of the cervical and lumbar generators in vitro by sucrose blockade at the thoracic cord level revealed independent rhythmogenic capabilities with similar cycle frequencies in the two locomotor regions. When the cord was partitioned at different thoracic levels and 5-HT/NMA/DA was applied to the more caudal compartment, the ability of the lumbar generators to drive their cervical counterparts increased with the proportion of chemically exposed thoracic segments. Blockade of synaptic inhibition at the lumbar level caused synchronous bilateral lumbar rhythmicity that, surprisingly, also was able to impose bilaterally synchronous bursting at the unblocked cervical level. Furthermore, after a midsagittal section from spinal segments C1 to T7, and during additional blockade of cervical synaptic inhibition, the cord exposed to 5-HT/NMA/DA continued to produce a coordinated fictive walking pattern similar to that observed in control. Thus, in the newborn rat, a caudorostral propriospinal excitability gradient appears to mediate interlimb coordination, which relies more on asymmetric axial connectivity (both excitatory and inhibitory) between the lumbar and cervical generators than on differences in their inherent rhythmogenic capacities.

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“…For instance, quipazine (5-HT 2 agonist) and L-DOPA were found to generate greater effects on hindlimb movement induction when coadministered in Tx rats (McEwen et al 1997) and mice (Guertin 2004a;Landry and Guertin 2004). Quipazine-induced air-stepping was found to critically depend on glutamate receptor activation (i.e., endogenous glutamate release since blocked by in Tx mice (Guertin 2004b).…”

Section: Introductionmentioning

confidence: 99%

“…For instance, quipazine (5-HT 2 agonist) and L-DOPA were found to generate greater effects on hindlimb movement induction when coadministered in Tx rats (McEwen et al 1997) Ϫ/Ϫ ) mice were used to demonstrate a specific role in LM induction for both receptor subtypes (i.e., 5-HT 1A and 5-HT 7 ) in Tx animals (Landry et al 2006a). However, it remains unclear whether simultaneously activating some of these specific receptor subtypes in vivo may lead to synergistic actions on CPG activation and hindlimb movement induction.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of D_1/5 and 5-HT_1A/7 Receptor Agonists on Locomotor Movement Induction in Complete Spinal Cord–Transected Mice

Lapointe¹,

Guertin²

2008

Journal of Neurophysiology

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Lapointe NP, Guertin PA. Synergistic effects of D 1/5 and 5-HT 1A/7 receptor agonists on locomotor movement induction in complete spinal cord-transected mice. J Neurophysiol 100: 160 -168, 2008. First published May 14, 2008 doi:10.1152/jn.90339.2008. Monoamines are well known to modulate locomotion in several vertebrate species. Coapplication of dopamine (DA) and serotonin (5-HT) has also been shown to potently induce fictive locomotor rhythms in isolated spinal cord preparations. However, a synergistic contribution of these monoamines to locomotor rhythmogenesis in vivo has never been examined. Here, we characterized the effects induced by selective DA and 5-HT receptor agonists on hindlimb movement induction in completely spinal cord transected (adult) mice. Administration of the lowest effective doses of SKF-81297 (D 1/5 agonist, 1-2 mg/kg, ip) or 8-OH-DPAT (5-HT 1A/7 agonist, 0.5 mg/kg, ip) acutely elicited some locomotor-like movements (LM) (5.85 Ϯ 1.22 and 3.67 Ϯ 1.44 LM/min, respectively). Coadministration of the same doses of SKF-81297 and 8-OH-DPAT led to a significant increase (7-to 10-fold) of LM (37.70 Ϯ 5.01 LM/min). Weight-bearing and plantar foot placement capabilities were also found with the combination treatment only (i.e., with no assistance or other forms of stimulation). These results clearly show that D 1/5 and 5-HT 1A/7 receptor agonists can synergistically activate spinal locomotor networks and thus generate powerful basic stepping movements in complete paraplegic animals. Although previous work from this laboratory has reported the partial rhythmogenic potential of monoamines in vivo, the present study shows that drug combinations such as SKF-81297 and 8-OH-DPAT can elicit weight-bearing stepping. I N T R O D U C T I O NThe existence of a neuronal network capable of generating the basic commands for walking has been clearly demonstrated several years ago in completely spinal cord-transected cats (preliminary evidence reported by Brown 1911; Grillner and Zangger 1979). Often referred to as the central pattern generator (CPG), this network-located for the most part in the lumbar spinal cord-was reported indeed to produce locomotor-like activity following systemic administration of levodopa (L-DOPA; L-3,4-dihydroxyphenylalanine) and nialamide (noradrenergic/dopaminergic precursor and monoamine oxidase inhibitor, respectively) in the complete absence of input from the brain and the periphery (low-thoracic-transected and rhizotomized cats; Grillner and Zangger 1979). Shortly after that discovery, a plethora of substances tested in acute or chronic paraplegic cats have provided data suggesting that several monoaminergic systems are involved in the control of locomotion (reviewed in Rossignol et al. 2001). Along this line of evidence, a role for monoaminergic neurotransmitters in locomotor functions was strongly supported by Gerin et al. (1995) who showed, using spinal cord-implanted microdialysis probes and chromatography, an increase of dopamine (DA) and serotonin (5-HT) release in the ventr...

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L-DOPA and quipazine elicit air-stepping in neonatal rats with spinal cord transections.

Cited by 47 publications

References 41 publications

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats

Propriospinal Circuitry Underlying Interlimb Coordination in Mammalian Quadrupedal Locomotion

Synergistic Effects of D_1/5 and 5-HT_1A/7 Receptor Agonists on Locomotor Movement Induction in Complete Spinal Cord–Transected Mice

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L-DOPA and quipazine elicit air-stepping in neonatal rats with spinal cord transections.

Cited by 47 publications

References 41 publications

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats

Kinematic analyses of air-stepping in normal and decerebrate preweanling rats

Propriospinal Circuitry Underlying Interlimb Coordination in Mammalian Quadrupedal Locomotion

Synergistic Effects of D1/5 and 5-HT1A/7 Receptor Agonists on Locomotor Movement Induction in Complete Spinal Cord–Transected Mice

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Synergistic Effects of D_1/5 and 5-HT_1A/7 Receptor Agonists on Locomotor Movement Induction in Complete Spinal Cord–Transected Mice