The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord

Schmidt, Brian J.; Jordan, Larry M.

doi:10.1016/s0361-9230(00)00402-0

Cited by 383 publications

(316 citation statements)

References 364 publications

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“…3A'). Increasing doses of mianserin did not have any significant effects on the H/M ratio in animals at 4wks after a complete transection, which resulted in complete depletion of serotonin in the lumbar spinal cord ( Fig.5C; Lee, et al, 2005,Fig.5C;Schmidt and Jordan, 2000).…”

Section: Effect Of Mianserin On the H-reflex After Scimentioning

confidence: 85%

“…Since virtually all serotonin in the spinal cord is of supraspinal origin (for review see Schmidt and Jordan, 2000), a midthoracic transection leads to a depletion of serotonin in the lower lumbar spinal cord as indicated by the complete absence of 5-HT immunoreactivity in this region ( Fig.5C; Hadjiconstantinou, et al, 1984, Lee, et al, 2005. Therefore, the lack of any significant effects of increasing doses of mianserin on the H/M ratio of transected rats indicated that the effect of mianserin observed in contused rats was not due to any non-specific interactions with local lumbar circuitry.…”

Section: Discussionmentioning

confidence: 99%

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Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

Lee

Johnson

Wrathall

2007

Experimental Neurology

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The amplitude of the H-reflex increases chronically after incomplete SCI and is associated with the development of exaggerated hindlimb reflexes. Although the mechanism for this increased H-reflex is not clear, previous studies have shown that pharmacological activation of the 5-HT 2 receptors (5-HT 2 R) can potentiate the monosynaptic reflex. This study tested the hypothesis that increased expression of 5-HT 2 R on motoneurons is involved in increased H-reflex amplitude after a standardized clinically-relevant contusive SCI. Adult female rats were subjected to contusion, complete surgical transection, or a T8 laminectomy only. At 4wks after surgery, H-reflex recordings from the hindpaw plantar muscles of contused rats showed twice the amplitude of that in laminectomy controls or transected rats. To probe the role of 5-HT 2 R in this increased amplitude, dose response studies were done with the selective antagonists, mianserin or LY53857, and the 5-HT 2 R agonist, (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI). The drugs were intrathecally infused into the lumbar cord while recording the H-reflex. Mianserin did not have any significant effects on the H-reflex after transection, consistent with the loss of distal serotonergic innervation. After contusion, both 5-HT 2 R antagonists reduced the H-reflex reflex amplitude with a significantly higher ID 50 compared to the uninjured controls. The 5-HT 2 R agonist, DOI, significantly increased reflex amplitude in contused but not control rats. Furthermore, while 5-HT immunoreactivity was similar, contused rats displayed increased 5-HT 2A R immunoreactivity in plantar muscle motoneurons compared to uninjured controls. We conclude that increased expression of 5-HT 2 R is likely to be involved in the enhanced H-reflex that develops after contusive SCI.

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Section: Effect Of Mianserin On the H-reflex After Scimentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

Lee

Johnson

Wrathall

2007

Experimental Neurology

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“…Our observations on the rostro-caudal gradient of 5-HT, 5-HIAA and NA confirm earlier data obtained for the rats [20][21][22] and for the cats. 23 Although there is no clear correlation between distribution of monoamines and their receptors along the spinal cord, [24][25][26][27] there are indications that the density of 5-HT 7 receptor, which is implicated in the control of locomotion, is higher in the rostral than in caudal lumbar segments. [26][27][28] Recently, the data obtained in isolated neonatal mouse spinal cord preparations by Christie and Whelan 29 revealed that combinations of monoaminergic compounds established a rostro-caudal organization of locomotor rhythms.…”

Section: Discussionmentioning

confidence: 99%

Different effect of locomotor exercise on the homogenate concentration of amino acids and monoamines in the rostral and caudal lumbar segments of the spinal cord in the rat

et al. 2006

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Study design: The effect of long-term (4 weeks) moderate locomotor exercise on segmental distribution of glutamate (Glu), aspartate, gamma-aminobutyric acid, glycine (Gly), serotonin and noradrenaline in the spinal cord of adult rats was investigated. Objectives: In light of the data showing modulation of some neurotransmitters in the lowlumbar segments of the rat due to physical exercise, our aim was to establish how segmentally specific is this effect with respect to neuroactive amino acids and monoamines. Setting: Laboratory of Reinnervation Processes, Department of Neurophysiology, Nencki Institute of Experimental Biology, Warsaw, Poland. Methods: Amino acids and monoamines content was measured by means of HPLC in the whole tissue homogenate of the spinal cord in nonexercised and exercised rats. Results: Glu and Gly homogenate concentration was the highest among all tested compounds. There was an intersegmental rostro-caudal gradient of concentration of neuroactive amino acids and monoamines, progressing caudally. Exercise modified this gradient exerting opposite effect on their concentration of amino acids and monoamines in the rostral and caudal lumbar segments. Conclusion: Locomotor exercise leads to neurochemical remodeling of the spinal cord, which is differently manifested in the rostral and caudal lumbar segments of the spinal cord.

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“…We believe this increased spasticity may be related to elevated descending 5-HT pathways during repetitive rhythmic MVCs, 22 which provided a greater substrate for action of the SSRIs. The resulting 5-HT modulation of spinal circuits 24 could result in depolarization of motoneurons and selected interneurons and amplification of persistent inward currents, 25,47,48 thereby increasing motor output with specific afferent inputs.…”

Section: Effects Of Ssris On Stretch Reflex Excitabilitymentioning

confidence: 99%

“…22,23 While the central effects of 5-HT are complex, the net result on motor systems is excitatory. 24,25 In humans poststroke, most studies using SSRIs or other 5-HT reuptake inhibitors (eg, fluoxetine, paroxetine, venlafaxine) focus on the upper extremity and indicate enhanced cortical excitability and motor performance in subacute and chronic stroke (grip strength, rate of finger tap, and 9-hole peg test 17,20,26 ). Interestingly, with repeated SSRI administration, data from intact individuals demonstrate potential decreased motor cortical excitability, 27,28 while studies 19,29 with patients early poststroke undergoing rehabilitation indicate improved motor recovery.…”

mentioning

confidence: 99%

Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke

Gourab

Schmit

Hornby

2015

Archives of Physical Medicine and Rehabilitation

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The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord

Cited by 383 publications

References 364 publications

Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

Up-regulation of 5-HT2 receptors is involved in the increased H-reflex amplitude after contusive spinal cord injury

Different effect of locomotor exercise on the homogenate concentration of amino acids and monoamines in the rostral and caudal lumbar segments of the spinal cord in the rat

Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke

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